Academic literature on the topic 'RNA-induced silencing complex (RISC)'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'RNA-induced silencing complex (RISC).'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "RNA-induced silencing complex (RISC)"
1
NIKOLOV, SVETOSLAV, and VALKO PETROV. "TIME DELAY MODEL OF RNA SILENCING." Journal of Mechanics in Medicine and Biology 07, no. 03 (2007): 297–314. http://dx.doi.org/10.1142/s0219519407002315.
Full textAbstract:
RNA silencing (also known as RNA interference) suppresses the expression of genes posttranscriptionally. We propose a time delay model of RNA silencing through a system consisting of double-stranded RNA (dsRNA), RNA-induced silencing complex (RISC), messenger RNA (mRNA), and RISC–mRNA complex. The time delay model is based on the consideration that the regeneration (or degradation) of the RISC–mRNA complex needs a finite time τ. The model equations are analyzed using nonlinear dynamics methods, in particular the Hopf bifurcation theorem, and they are solved numerically. From the accomplished analytical and numerical calculations, it becomes clear that time delay τ is a key factor in the behavior of the model. In this case, it has a destabilizing effect on the silencing process.
2
Prakash, Prerana, and M. G. Hariprasad. "SIRNA: ITS TRANSLATIONFROM RESEARCH TO THERAPEUTIC APPLICATIONS." International Journal of Advanced Research 13, no. 05 (2025): 538–43. https://doi.org/10.21474/ijar01/20930.
Full textAbstract:
Small interfering RNA (siRNA) is a short, double-stranded RNA molecule that has emerged as a pivotal tool for gene silencing through the RNA interference (RNAi) pathway. It is a powerful post-transcriptional gene-silencing molecule central to RNA interference (RNAi) mechanisms1. Typically 21–25 nucleotides in length, it guides the RNA-induced silencing complex (RISC) to a target messenger RNA (mRNA), enabling sequence-specific degradation and effectively silencing gene expression2. This process is highly specific and forms the foundation for siRNA’s role in research and therapeutic interventions3. By guiding the RNA-induced silencing complex (RISC) to target mRNA, siRNA enables post-transcriptional gene regulation with unparalleled precision. This targeted action holds immense promise in treating genetic, infectious, and degenerative diseases4. Therapeutically, siRNA offers unique advantages over traditional treatments, including the ability to target undruggable proteins, rapid development timelines, and reduced systemic toxicity. These advantages have catalyzed interest in siRNA for precision medicine and rare genetic disorders5
3
Pantaleo, Vitantonio, György Szittya, and József Burgyán. "Molecular Bases of Viral RNA Targeting by Viral Small Interfering RNA-Programmed RISC." Journal of Virology 81, no. 8 (2007): 3797–806. http://dx.doi.org/10.1128/jvi.02383-06.
Full textAbstract:
ABSTRACT RNA silencing is conserved in a broad range of eukaryotes and operates in the development and maintenance of genome integrity in many organisms. Plants have adapted this system for antiviral defense, and plant viruses have in turn developed mechanisms to suppress RNA silencing. RNA silencing-related RNA inactivation is likely based on target RNA cleavage or translational arrest. Although it is widely assumed that virus-induced gene silencing (VIGS) promotes the endonucleolytic cleavage of the viral RNA genome, this popular assumption has never been tested experimentally. Here we analyzed the viral RNA targeting by VIGS in tombusvirus-infected plants, and we show evidence that antiviral response of VIGS is based on viral RNA cleavage by RNA-induced silencing effector complex (RISC) programmed by virus-specific small interfering RNAs (siRNAs). In addition, we found that the RISC-mediated cleavages do not occur randomly on the viral genome. Indeed, sequence analysis of cloned cleavage products identified hot spots for target RNA cleavage, and the regions of specific RISC-mediated cleavages are asymmetrically distributed along the positive- and negative-sense viral RNA strands. In addition, we identified viral siRNAs containing high-molecular-mass protein complexes purified from the recovery leaves of the silencing suppressor mutant virus-infected plants. Strikingly, these large nucleoproteins cofractionated with microRNA-containing complexes, suggesting that these nucleoproteins are silencing related effector complexes.
4
Nitin, B. Ghiware Pawan Wankhade Sangameshwar B. Kanthale Ajay D. Kshirsagar Haidarali M. Shaikh*. "REGULATION OF MICRO-RNA IN CANCER." INDO AMERICAN JOURNAL OF PHARMACEUTICAL SCIENCES 05, no. 01 (2018): 502–9. https://doi.org/10.5281/zenodo.1161661.
Full textAbstract:
Cancer is a dreadful disease of mankind, the treatment for cancer is not revealed as per expectation. The illuminating way come out with understanding and grab the molecular alteration in cell. Therefore, miRNAs is a novel notation for procurement of cancer. MicroRNAs are small, highly conserved non-coding RNA molecules involved in the regulation of gene expression. MicroRNAs are transcribed by RNA polymerases II and III which forms precursors that undergoes series of cleavage to form mature microRNA. There are two types of biogenesis pathways, one nuclear and one cytoplasmic. However there are some alternative biogenesis pathways exist that differ from conventional pathway in the number of cleavage events and enzymes responsible. The mechanism of sorting of microRNA precursors to the different pathways is unclear but it can be determined by the site of origin, its sequence and thermodynamic stability. The regulatory functions of microRNAs are able through the RNA-induced silencing complex (RISC). The regulation level of miRNAs in cell i.e. up regulation and down regulation, leads to cancer. In this review, highlighted the role of miRNAs in physiological way and explain the molecular mechanism involved in development of cancer. Key words:MicroRNA, Cancer, RNA-induced silencing complex (RISC), RNA polymerases II and III.
5
Martínez-Turiño, Sandra, and Carmen Hernández. "Inhibition of RNA silencing by the coat protein of Pelargonium flower break virus: distinctions from closely related suppressors." Journal of General Virology 90, no. 2 (2009): 519–25. http://dx.doi.org/10.1099/vir.0.006098-0.
Full textAbstract:
Viral-derived double-stranded RNAs (dsRNAs) activate RNA silencing, generating small interfering RNAs (siRNAs) which are incorporated into an RNA-induced silencing complex (RISC) that promotes homology-dependent degradation of cognate RNAs. To counteract this, plant viruses express RNA silencing suppressors. Here, we show that the coat protein (CP) of Pelargonium flower break virus (PFBV), a member of the genus Carmovirus, is able to efficiently inhibit RNA silencing. Interestingly, PFBV CP blocked both sense RNA- and dsRNA-triggered RNA silencing and did not preclude generation of siRNAs, which is in contrast with the abilities that have been reported for other carmoviral CPs. We have also found that PFBV CP can bind siRNAs and that this ability correlates with silencing suppression activity and enhancement of potato virus X pathogenicity. Collectively, the results indicate that PFBV CP inhibits RNA silencing by sequestering siRNAs and preventing their incorporation into a RISC, thus behaving similarly to unrelated viral suppressors but dissimilarly to orthologous ones.
6
Deshpande, Sonal, and Neetu Singh. "Probing the nanoparticle–AGO2 interaction for enhanced gene knockdown." Soft Matter 14, no. 20 (2018): 4169–77. http://dx.doi.org/10.1039/c8sm00534f.
Full textAbstract:
RNA interference is a promising technology for treatment of various diseases. Here, we systematically probe the effect of steric hindrance of nanoparticles on the RNA induced silencing complex (RISC) interaction, by modulating two parameters, the nanoparticle size and hardness.
7
Itaya, Asuka, Xuehua Zhong, Ralf Bundschuh, et al. "A Structured Viroid RNA Serves as a Substrate for Dicer-Like Cleavage To Produce Biologically Active Small RNAs but Is Resistant to RNA-Induced Silencing Complex-Mediated Degradation." Journal of Virology 81, no. 6 (2007): 2980–94. http://dx.doi.org/10.1128/jvi.02339-06.
Full textAbstract:
ABSTRACT RNA silencing is a potent means of antiviral defense in plants and animals. A hallmark of this defense response is the production of 21- to 24-nucleotide viral small RNAs via mechanisms that remain to be fully understood. Many viruses encode suppressors of RNA silencing, and some viral RNAs function directly as silencing suppressors as counterdefense. The occurrence of viroid-specific small RNAs in infected plants suggests that viroids can trigger RNA silencing in a host, raising the question of how these noncoding and unencapsidated RNAs survive cellular RNA-silencing systems. We address this question by characterizing the production of small RNAs of Potato spindle tuber viroid (srPSTVds) and investigating how PSTVd responds to RNA silencing. Our molecular and biochemical studies provide evidence that srPSTVds were derived mostly from the secondary structure of viroid RNAs. Replication of PSTVd was resistant to RNA silencing, although the srPSTVds were biologically active in guiding RNA-induced silencing complex (RISC)-mediated cleavage, as shown with a sensor system. Further analyses showed that without possessing or triggering silencing suppressor activities, the PSTVd secondary structure played a critical role in resistance to RISC-mediated cleavage. These findings support the hypothesis that some infectious RNAs may have evolved specific secondary structures as an effective means to evade RNA silencing in addition to encoding silencing suppressor activities. Our results should have important implications in further studies on RNA-based mechanisms of host-pathogen interactions and the biological constraints that shape the evolution of infectious RNA structures.
8
Pashupathi, M. and Rashmi Mishra. "RNA Interference in Veterinary Parasitology." Vet Farm Frontier 02, no. 04 (2025): 155–56. https://doi.org/10.5281/zenodo.15401258.
Full textAbstract:
<strong>Introduction</strong> RNA interference (RNAi) is a naturally occurring mechanism of gene silencing that regulates gene expression post-transcriptionally. This process utilizes small double-stranded RNA molecules—particularly small interfering RNAs (siRNAs) and microRNAs (miRNAs)—to bind complementary sequences on target messenger RNAs (mRNAs), ultimately preventing their translation into proteins. Initially observed in plants and later in nematodes, the discovery of RNAi fundamentally changed our understanding of gene regulation and introduced a powerful tool for genetic research and therapy. <strong>Discovery and Mechanism of Action</strong> The landmark discovery of RNA interference was made in the nematode <em>Caenorhabditis elegans</em> by scientists Andrew Fire and Craig Mello in 1998. Their research demonstrated that the injection of double-stranded RNA (dsRNA) could lead to the silencing of genes with matching sequences. This discovery earned them the Nobel Prize in Physiology or Medicine in 2006. The process of RNAi begins with the introduction or endogenous production of dsRNA, which is cleaved by the RNase III enzyme Dicer into short fragments known as siRNAs. These siRNAs are then loaded into the RNA-induced silencing complex (RISC), guiding the complex to the target mRNA through sequence complementarity. Once bound, the RISC complex cleaves the mRNA, leading to its degradation and silencing of gene expression.
9
Yoo, Byoung Kwon, Prasanna K. Santhekadur, Rachel Gredler, et al. "Increased RNA-induced silencing complex (RISC) activity contributes to hepatocellular carcinoma." Hepatology 53, no. 5 (2011): 1538–48. http://dx.doi.org/10.1002/hep.24216.
Full text
10
Piao, Xianghua, Xue Zhang, Ligang Wu, and Joel G. Belasco. "CCR4-NOT Deadenylates mRNA Associated with RNA-Induced Silencing Complexes in Human Cells." Molecular and Cellular Biology 30, no. 6 (2010): 1486–94. http://dx.doi.org/10.1128/mcb.01481-09.
Full textAbstract:
ABSTRACT MicroRNAs (miRNAs) repress gene expression posttranscriptionally by inhibiting translation and by expediting deadenylation so as to trigger rapid mRNA decay. Their regulatory influence is mediated by the protein components of the RNA-induced silencing complex (RISC), which deliver miRNAs and siRNAs to their mRNA targets. Here, we present evidence that CCR4-NOT is the deadenylase that removes poly(A) from messages destabilized by miRNAs in human cells. Overproducing a mutationally inactivated form of either of the catalytic subunits of this deadenylase (CCR4 or CAF1/POP2) significantly impedes the deadenylation and decay of mRNA targeted by a partially complementary miRNA. The same deadenylase initiates the degradation of “off-target” mRNAs that are bound by an imperfectly complementary siRNA introduced by transfection. The greater inhibitory effect of inactive CAF1 or POP2 (versus inactive CCR4) suggests a predominant role for this catalytic subunit of CCR4-NOT in miRNA- or small interfering RNA (siRNA)-mediated deadenylation. These effects of mi/siRNAs and CCR4-NOT can be fully reproduced by directly tethering RISC to mRNA without the guidance of a small RNA, indicating that the ability of RISC to accelerate deadenylation is independent of RNA base pairing. Despite its importance for mi/siRNA-mediated deadenylation, CCR4-NOT appears not to associate significantly with RISC, as judged by the failure of CAF1 and POP2 to coimmunoprecipitate detectably with either the Ago or TNRC6 subunit of RISC, a finding at odds with deadenylase recruitment as the mechanism by which RISC accelerates poly(A) removal.
Dissertations / Theses on the topic "RNA-induced silencing complex (RISC)"
1
Matranga, Christian B. "Understanding Assembly of AGO2 RISC: the RNAi enzyme: a Dissertation." eScholarship@UMMS, 2007. https://escholarship.umassmed.edu/gsbs_diss/347.
Full textAbstract:
In 1990, Richard Jorgensen’s lab initiated a study to test if they could create a more vivid color petunia (Napoli et al. 1990). Their plan was to transform plants with the chalcone synthase transgene––the predicted rate limiting factor in the production of purple pigmentation. Much to their surprise, the transgenic plants, as well as their progeny, displayed a great reduction in pigmentation. This loss of endogenous function was termed “cosuppression” and it was thought that sequence-specific repression resulted from over-expression of the homologous transgene sequence. In 1998, Andrew Fire and Craig Mello described a phenomenon in which double stranded RNA (dsRNA) can trigger silencing of cognate sequences when injected into the nematode, Caenorhabditis elegans (Fire et al. 1998). This data explained observations seen years earlier by other worm researchers, and suggested that repression of pigmentation in plants was caused by a dsRNA-intermediate (Guo and Kemphues 1995; Napoli et al. 1990). The phenomenon––which soon after was coined RNA interference (RNAi)––was soon discovered to be a post-transcriptional surveillance system in plants and animals to remove foreign nucleic acids.
2
Chu, Chia-Ying. "Molecular Mechanism of RNA-Mediated Gene Silencing in Human Cells: A Dissertation." eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/388.
Full textAbstract:
Small non-coding RNAs regulate gene expression at posttranscriptional level in eukaryotic cells. Two classes of such small (~21-25 nt) RNAs that have been extensively studied in gene silencing are short interfering RNAs (siRNAs) and microRNAs (miRNAs). RNA interference (RNAi) is process whereby double-stranded RNA induces the sequence-specific degradation of homologous mRNA. The RNAi machinery can also be programmed in human cells by introducing 21-nt siRNA duplexes that are assembled into RNA-induced silencing complexes (RISC). In this dissertation, systematic analysis of siRNAs with deletions at the passenger and/or guide strand reveals that a short RNAi trigger, 16-nt siRNA, induces potent RNAi in human cells. The 16-nt siRNA more effectively knocked down mRNA and protein levels than 19-nt siRNA when targeting the endogenous CDK9 gene. In vitro kinetic analysis of human RISC indicates that 16-nt siRNA has a higher RISC-loading capacity than 19-nt siRNA. These results suggest that 16-nt duplexes can be designed as potent triggers for RNAi.
RISC can be programmed by small interfering RNAs (siRISC) to cleave a perfectly complementary target mRNA, or endogenous microRNAs (miRISC) to inhibit translation by binding imperfectly matched sequences in the 3’-untranslated region (3’-UTR) of target mRNA. Both RISCs contain Argonaute2 (Ago2), which localizes to cytoplasmic mRNA processing P-bodies. This dissertation shows that RCK/p54, a DEAD box helicase, interacts with Ago2, in affinity-purified active siRISC or miRISC, facilitates formation of P-bodies. Depletion of RCK/p54 disrupted P-bodies and dispersed Ago2 throughout the cytoplasm, but did not significantly affect siRNA-mediated RNAi. Depleting RCK/p54 releases general and miRNA-induced translational repression. These findings imply that miRISC-mediated translation repression requires RCK/p54, also suggest that location of miRISC to P-bodies is not required for miRNA function, but is the consequence of translation repression.
To elucidate the function of RCK/p54 in miRNA-mediated gene silencing, analysis of a series of YFP-tagged RCK/p54 mutants reveals the motif required for P-body localization, interaction with Ago2, and/or facilitating the miRNA-mediated translation repression. Additionally, rabbit reticulocyte lysate system was used to recapitulate the miRISC function in a cell-free system and confirmed the requirement of RCK/p54 for miRNA function in vitro. Analysis of Ago2 distribution in the polysome profiling in RCK/p54-depleted cells, compared to that in normal cells, revealed that RCK/p54 facilitates miRISC by trapping it at translation initiation complex. These data suggest that interaction of RCK/p54 with Ago2 is involved in the repression of translation initiation of miRNA function.
3
Howard-Till, Rachel A. "Small RNA pathways and the roles of tudor nucleases in gene silencing and DNA deletion in Tetrahymena thermopila /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/5064.
Full text
4
Broderick, Jennifer A. "Cooperativity in Mammalian RNA Silencing: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/548.
Full textAbstract:
Argonaute proteins are the core component of an RNA silencing complex. The human genome encodes four Argonaute paralogs –Ago1, Ago2, Ago3 and Ago4– proteins that are guided to target mRNAs by microRNAs. More than 500 miRNAs are conserved between mammals, and each microRNA can repress hundreds of genes, regulating almost every cellular process. We still do not fully understand the molecular mechanisms by which miRNAs regulate gene expression. Although we understand many aspects of microRNA biogenesis and formation of the RNA-induced silencing complex, much less is known about the subsequent steps leading to target mRNA regulation.
Mammalian microRNAs rarely have complete complementarity to their target mRNAs so, instead of endonucleolytic cleavage by Ago2, microRNAs destabilize or repress translation of target mRNAs. Here I explored the functional limits of Argonaute proteins bound to their targets directly and indirectly through microRNAs in mammalian cells. I revealed the different abilities for Argonaute proteins bound at multiple sites in a target to generate cooperativity in silencing based on the extent of pairing between the microRNA and target mRNA. Further, I harnessed the endogenous microRNA silencing mechanism to repress an mRNA that is not a direct target of the microRNA by tethering the RNA-induced silencing complex to the 3´ UTR of an mRNA. This strategy allows tissue-specific gene silencing due to the limited endogenous expression profile of the recruited microRNA. Efforts made herein further our mechanistic knowledge of microRNA-induced gene silencing in mammalian cells and advance microRNA-based strategies toward treating human disease.
5
Sigova, Alla A. "RNA Silencing Pathways in Schizosaccharomyces pombe and Drosophila melanogaster: A Dissertation." eScholarship@UMMS, 2006. https://escholarship.umassmed.edu/gsbs_diss/225.
Full textAbstract:
RNA silencing is an evolutionary conserved sequence-specific mechanism of regulation of gene expression. RNA interference (RNAi), a type of RNA silencing in animals, is based on recognition and endonucleolytic cleavage of target mRNA complimentary in sequence to 21-nucleotide (nt) small RNA guides, called small interfering RNAs (siRNAs). Another class of 21-nt small RNAs, called micro RNAs (miRNAs), is endogenously encoded in eukaryotic genomes. Both production of siRNAs from long double-stranded RNA (dsRNA) and biogenesis of miRNAs from hairpin structures are governed by the ribonuclease III enzyme Dicer. Although produced as duplex molecules, siRNAs and miRNAs are assembled into effector complex, called the RNA-induced silencing complex (RISC), as single-strands. A member of the Argonaute family of small RNA-binding proteins lies at the core of all known RNA silencing effector complexes. Plants and animals contain multiple Argonaute paralogs. In addition to endonucleolytic cleavage, Argonaute proteins can direct translational repression/destabilization of mRNA or transcriptional silencing of DNA sequences by the siRNAdirected production of silent heterochromatin.
The Schizosaccharomyces pombe genome encodes only one of each of the three major classes of proteins implicated in RNA silencing: Dicer (Dcr1), RNA-dependent RNA polymerase (RdRP; Rdp1), and Argonaute (Ago1). These three proteins are required for silencing at centromeres and for the initiation of transcriptionally silent heterochromatin at the mating-type locus. That only one Dicer, RdRP and Argonaute is expressed in S. pombe might reflect the extreme specialization of RNA silencing pathways regulating targets only at the transcriptional level in this organism. We decided to test if classical RNAi can be induced in S. pombe. We introduced a dsRNA hairpin corresponding to a GFP transgene. GFP silencing triggered by dsRNA reflected a change in the steady-state concentration of GFP mRNA, but not in the rate of GFP transcription. RNAi in S. pombe required dcr1, rdp1, and ago1, but did not require chp1, tas3, or swi6, genes required for transcriptional silencing. We concluded that the RNAi machinery in S. pombecould direct both transcriptional and posttranscriptional silencing using a single Dicer, RdRP, and Argonaute protein. Our findings suggest that, in spite of specialization in distinct siRNA-directed silencing pathways, these three proteins fulfill a common biochemical function.
In Drosophila, miRNA and RNAi pathways are both genetically and biochemically distinct. Dicer-2 (Dcr-2) generates siRNAs, whereas the Dicer-1 (Dcr-1)/Loquacious complex produces miRNAs. Argonaute proteins can be divided by sequence similarity into two classes: in flies, the Ago subfamily includes Argonaute1 (Ago1) and Argonaute2 (Ago2), whereas the Piwi subfamily includes Aubergine, Piwi and Argonaute 3. siRNAs and miRNAs direct posttranscriptional gene silencing through effector complexes containing Ago1 or Ago2. The third class of small RNAs, called repeat-associated small interfering RNAs (rasiRNAs), is produced endogenously in the Drosophilagerm line. rasiRNAs mediate silencing of endogenous selfish genetic elements such as retrotransposons and repetitive sequences to ensure genomic stability.
We examined the genetic requirements for biogenesis of rasiRNAs in both male and female germ line of Drosophilaand silencing of 8 different selfish elements, including tree LTR retrotransposons, two non-LTR retrotransposons, and three repetitive sequences. We find that biogenesis of rasiRNAs is different from that of miRNAs and siRNAs. rasiRNA production appears not to require Dicer-1 or Dicer-2. rasiRNAs lack the 2´,3´ hydroxy termini characteristic of animal siRNA and miRNA. While siRNAs derive from both the sense and antisense strands of their dsRNA precursors, rasiRNAs accumulate in antisense polarity to their corresponding target mRNAs. Unlike siRNAs and miRNAs, rasiRNAs function through the Piwi, rather than the Ago, Argonaute protein subfamily. We find that rasiRNAs silence their target RNAs posttranscriptionally: mutations that abrogate rasiRNA function dramatically increase the steady-state mRNA level of rasiRNA targets, but do not alter their rate of transcription, measured by nuclear run-on assay.
Our data suggest that rasiRNAs protect the fly germ line through a silencing mechanism distinct from both the miRNA and RNAi pathways.
6
Guidi, Mònica. "Micro RNA-Mediated regulation of the full-length and truncated isoforms of human neurotrophic tyrosine kinase receptor type 3 (NTRK 3)." Doctoral thesis, Universitat Pompeu Fabra, 2009. http://hdl.handle.net/10803/7114.
Full textAbstract:
Neurotrophins and their receptors are key molecules in the development of the<br/>nervous system. Neurotrophin-3 binds preferentially to its high-affinity receptor<br/>NTRK3, which exists in two major isoforms in humans, the full-length kinaseactive<br/>form (150 kDa) and a truncated non-catalytic form (50 kDa). The two<br/>variants show different 3'UTR regions, indicating that they might be differentially<br/>regulated at the post-transcriptional level. In this work we explore how<br/>microRNAs take part in the regulation of full-length and truncated NTRK3,<br/>demonstrating that the two isoforms are targeted by different sets of microRNAs.<br/>We analyze the physiological consequences of the overexpression of some of the<br/>regulating microRNAs in human neuroblastoma cells. Finally, we provide<br/>preliminary evidence for a possible involvement of miR-124 - a microRNA with no<br/>putative target site in either NTRK3 isoform - in the control of the alternative<br/>spicing of NTRK3 through the downregulation of the splicing repressor PTBP1.<br>Las neurotrofinas y sus receptores constituyen una familia de factores cruciales<br/>para el desarrollo del sistema nervioso. La neurotrofina 3 ejerce su función<br/>principalmente a través de una unión de gran afinidad al receptor NTRK3, del cual<br/>se conocen dos isoformas principales, una larga de 150KDa con actividad de tipo<br/>tirosina kinasa y una truncada de 50KDa sin dicha actividad. Estas dos isoformas<br/>no comparten la misma región 3'UTR, lo que sugiere la existencia de una<br/>regulación postranscripcional diferente. En el presente trabajo se ha explorado<br/>como los microRNAs intervienen en la regulación de NTRK3, demostrando que las<br/>dos isoformas son reguladas por diferentes miRNAs. Se han analizado las<br/>consecuencias fisiológicas de la sobrexpresión de dichos microRNAs utilizando<br/>células de neuroblastoma. Finalmente, se ha estudiado la posible implicación del<br/>microRNA miR-124 en el control del splicing alternativo de NTRK3 a través de la<br/>regulación de represor de splicing PTBP1.
7
Xu, Yunhe. "Molecular and diagnostic aspects of the protein p41 of HHV-6 and silencing of the CD46 receptor by RNA interference /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-553-0.
Full text
8
Horwich, Michael D. "Small RNA Sorting in Drosophila Produces Chemically Distinct Functional RNA-Protein Complexes: A Dissertation." eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/384.
Full textAbstract:
Small interfering RNAs (siRNAs), microRNAs (miRNAs), and piRNAs (piRNA) are conserved classes of small single-stranded ~21-30 nucleotide (nt) RNA guides that repress eukaryotic gene expression using distinct RNA Induced Silencing Complexes (RISCs). At its core, RISC is composed of a single-stranded small RNA guide bound to a member of the Argonaute protein family, which together bind and repress complementary target RNA. miRNAs target protein coding mRNAs—a function essential for normal development and broadly involved in pathways of human disease; small interfering RNAs (siRNA) defend against viruses, but can also be engineered to direct experimental or therapeutic gene silencing; piwi associated RNAs (piRNAs) protect germline genomes from expansion of parasitic nucleic acids such as transposons. Using the fruit fly, Drosophila melanogaster, as a model organism we seek to understand how small silencing RNAs are made and how they function.
In Drosophila, miRNAs and siRNAs are proposed to have parallel, but separate biogenesis and effector machinery. miRNA duplexes are excised from imperfectly paired hairpin precursors by Dicer1 and loaded into Ago1; siRNA duplexes are hewn from perfectly paired long dsRNA by Dicer2 and loaded into Ago2. Contrary to this model we found one miRNA, miR-277, is made by Dicer1, but partitions between Ago1 and Ago2 RISCs. These two RISCs are functionally distinct—Ago2 could silence a perfectly paired target, but not a centrally bulged target; Ago1 could silence a bulged target, but not a perfect target. This was surprising since both Ago1 and Ago2 have endonucleolytic cleavage activity necessary for perfect target cleavage in vitro. Our detailed kinetic studies suggested why—Ago2 is a robust multiple turnover enzyme, but Ago1 is not. Along with a complementary in vitro study our data supports a duplex sorting mechanism in which Diced duplexes are released, and rebind to Ago1 or Ago2 loading machinery, regardless of which Dicer produced them. This allows structural information embedded in small RNA duplexes to direct small RNA loading into Ago1 and/or Ago2, resulting in distinct regulatory outputs.
Small RNA sorting also has chemical consequences for the small RNA guide. Although siRNAs were presumed to have the signature 2′, 3′ hydroxyl ends left by Dicer, we found that small RNAs loaded into Ago2 or Piwi proteins, but not Ago1, are modified at their 3´ ends by the RNA 2´-O-methyltransferase DmHen1. In plants Hen1 modifies the 3´ ends all small RNAs duplexs, protecting and stabilizing them. Implying a similar function in flies, piRNAs are smaller, less abundant, and their function is perturbed in hen1 mutants. But unlike plants, small RNAs are modified as single-strands in RISC rather than as duplexes. This nicely explains why the dsRNA binding domain in plant Hen1 was discarded in animals, and why both dsRNA derived siRNAs and ssRNA derived piRNAs are modified. The recent discovery that both piRNAs and siRNAs target transposons links terminal modification and transposon silencing, suggesting that it is specialized for this purpose.
9
Du, Tingting. "Dissecting Small RNA Loading Pathway in Drosophila melanogaster: A Dissertation." eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/356.
Full textAbstract:
In the preceding chapters, I have discussed my doctoral research on studying the siRNA loading pathway in Drosophila using both biochemical and genetic approaches. We established a gel shift system to identify the intermediate complexes formed during siRNA loading. We detected at least three complexes, named complex B, RISC loading complex (RLC) and RISC. Using kinetic modeling, we determined that the siRNA enters complex B and RLC early during assembly when it remains double-stranded, and then matures in RISC to generate Argonaute bearing only the single-stranded guide. We further characterized the three complexes. We showed that complex B comprises Dcr-1 and Loqs, while both RLC and RISC contain Dcr-2 and R2D2. Our study suggests that the Dcr-2/R2D2 heterodimer plays a central role in RISC assembly. We observed that Dcr-1/Loqs, which function together to process pre-miRNA into mature miRNA, were also involved in siRNA loading. This was surprising, because it has been proposed that the RNAi pathway and miRNA pathway are separate and parallel, with each using a unique set of proteins to produce small RNAs, to assemble functional RNA-guided enzyme complexes, and to regulate target mRNAs. We further examined the molecular function of Dcr-1/Loqs in RNAi pathway. Our data suggest that, in vivo and in vitro, the Dcr-1/Loqs complex binds to siRNA. In vitro, the binding of the Dcr-1/Loqs complex to siRNA is the earliest detectable step in siRNA-triggered Ago2-RISC assembly. Futhermore, the binding of Dcr-1/Loqs to siRNA appears to facilitate dsRNA dicing by Dcr-2/R2D2, because the dicing activity is much lower in loqslysate than in wild type.
Long inverted repeat (IR) triggered white silencing in fly eyes is an example of endogenous RNAi. Consistent with our finding that Dcr-1/Loqs function to load siRNA, less white siRNA accumulates in loqs mutant eyes compared to wild type. As a result, loqs mutants are partially defective in IR trigged whitesilencing. Our data suggest considerable functional and genetic overlap between the miRNA and siRNA pathways, with the two sharing key components previously thought to be confined to just one of the two pathways.
Based on our study on siRNA loading pathway, we also elucidated the molecular function of Armitage (Armi) protein in RNAi. We showed that armi is required for RNAi. Lysates from armi mutant ovaries are defective for RNAi in vitro. Native gel analysis of protein-siRNA complexes suggests that armi mutants support early steps in the RNAi pathway, i.e., the formation of complex B and RLC, but are defective in the production of the RISC.
10
Nhlabatsi, Neliswa. "Comparing the silencing efficacy of dicer-independent and dependent shRNAs." Thesis, 2015. http://hdl.handle.net/10539/17510.
Full textAbstract:
A dissertation submitted to the Faculty of Science, University of the Witwatersrand,
Johannesburg, in fulfilment of the requirements for the degree of Master of Science.
Johannesburg, 2014.<br>RNA interference (RNAi) is a highly conserved gene regulatory mechanism triggered by the presence of double-stranded RNAs and results in post-transcriptional and transcriptional gene silencing. RNAi has been demonstrated to have therapeutic potential to treat chronic viral infections including HIV-1. Due to the side effects of and eventual drug resistance to highly active antiretroviral therapy, a novel anti-HIV-1 therapy is required. The most suitable exogenous RNAi triggers to use in anti-HIV-1 RNAi-based therapy are expressed short hairpin RNAs (shRNAs). Despite being highly developed, shRNA systems still pose safety concerns. Highly expressed shRNAs are at risk of over-saturating the endogenous RNAi pathway, inducing an innate immune response or silencing off-target mRNA. The purpose of this study was to minimise shRNA-associated off-target effects and simultaneously maximise the potency and specificity of expressed shRNAs for potential therapeutic application. ShRNAs shorter than 19 base pairs are not recognised by the endonuclease Dicer, which is an important component of the RNAi pathway, but miR-451 is Dicer-independent. Smaller shRNAs that retain their potency would be easier to deliver into a disease model. For this study, 25mers and miR-451-mimicking 19mers were generated. The shRNA pairs exhibited significant knockdown of their respective targets in dual-luciferase assays. The 19mers are more specific gene silencers compared to the 25mers. A 19mer that is more potent than its 25mer counterpart was identified. None of the hairpins induced an innate immune response, caused cytotoxic effects or saturated the endogenous RNAi pathway. This study concludes that the 19mers were processed in a manner similar to miR-451 resulting in a single ~30 nt mature RNA product. We dubbed these miR-451-mimicking 19mers, guide shRNAs. The single RNA strand of mature guide shRNAs abolishes the risk sense strand-associated off-targeting thus improving shRNA specificity. These revolutionary guide shRNAs can be developed into highly potent activators of the RNAi pathway in a therapeutic setting.
Book chapters on the topic "RNA-induced silencing complex (RISC)"
1
Zhang, Yan. "RNA-induced Silencing Complex (RISC)." In Encyclopedia of Systems Biology. Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4419-9863-7_329.
Full text
2
Sand, Michael. "Paper 2: Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components argonaute-1, argonaute-2, PACT, TARBP1 and TARBP2 in epithelial skin cancer." In MicroRNAs in malignant tumors of the skin. Springer Fachmedien Wiesbaden, 2016. http://dx.doi.org/10.1007/978-3-658-12794-7_6.
Full text
3
Datta, Abhijit, and Sayak Ganguli. "The Interactomics of the RNA-Induced Silencing Complex." In Current trends in Bioinformatics: An Insight. Springer Singapore, 2018. http://dx.doi.org/10.1007/978-981-10-7483-7_11.
Full text
4
Caudy, Amy A., and Gregory J. Hannon. "Induction and Biochemical Purification of RNA-Induced Silencing Complex From Drosophila S2 Cells." In RNA Interference, Editing, and Modification. Humana Press, 2004. http://dx.doi.org/10.1385/1-59259-775-0:059.
Full text
5
Jones, Huw D. "Gene silencing or gene editing: the pros and cons." In RNAi for plant improvement and protection. CABI, 2021. http://dx.doi.org/10.1079/9781789248890.0006.
Full textAbstract:
Abstract Research into plant genetics often requires the suppression or complete knockout of gene expression to scientifically validate gene function. In addition, the phenotypes obtained from gene suppression can occasionally have commercial value for plant breeders. Until recently, the methodological choices to achieve these goals fell into two broad types: either some form of RNA-based gene silencing; or the screening of large numbers of natural or induced random genomic mutations. The more recent invention of gene editing as a tool for targeted mutation potentially gives researchers and plant breeders another route to block gene function. RNAi is widely used in animal and plant research and functions to silence gene expression by degrading the target gene transcript. Although RNAi offers unique advantages over genomic mutations, it often leads to the formation of a genetically modified organism (GMO), which for commercial activities has major regulatory and acceptance issues in some regions of the world. Traditional methods of generating genomic mutations are more laborious and uncertain to achieve the desired goals but possess a distinct advantage of not being governed by GMO regulations. Gene editing (GE) technologies have some of the advantages of both RNAi and classical mutation breeding in that they can be designed to give simple knockouts or to modulate gene expression more subtly. GE also has a more complex regulatory position, with some countries treating it as another conventional breeding method whilst the EU defines GE as a technique of genetic modification and applies the normal GMO authorization procedures. This chapter explores the pros and cons of RNAi alongside other methods of modulating gene function.
6
Jones, Huw D. "Gene silencing or gene editing: the pros and cons." In RNAi for plant improvement and protection. CABI, 2021. http://dx.doi.org/10.1079/9781789248890.0047.
Full textAbstract:
Abstract Research into plant genetics often requires the suppression or complete knockout of gene expression to scientifically validate gene function. In addition, the phenotypes obtained from gene suppression can occasionally have commercial value for plant breeders. Until recently, the methodological choices to achieve these goals fell into two broad types: either some form of RNA-based gene silencing; or the screening of large numbers of natural or induced random genomic mutations. The more recent invention of gene editing as a tool for targeted mutation potentially gives researchers and plant breeders another route to block gene function. RNAi is widely used in animal and plant research and functions to silence gene expression by degrading the target gene transcript. Although RNAi offers unique advantages over genomic mutations, it often leads to the formation of a genetically modified organism (GMO), which for commercial activities has major regulatory and acceptance issues in some regions of the world. Traditional methods of generating genomic mutations are more laborious and uncertain to achieve the desired goals but possess a distinct advantage of not being governed by GMO regulations. Gene editing (GE) technologies have some of the advantages of both RNAi and classical mutation breeding in that they can be designed to give simple knockouts or to modulate gene expression more subtly. GE also has a more complex regulatory position, with some countries treating it as another conventional breeding method whilst the EU defines GE as a technique of genetic modification and applies the normal GMO authorization procedures. This chapter explores the pros and cons of RNAi alongside other methods of modulating gene function.
7
"RISC (RNA-induced silencing complex)." In Encyclopedia of Genetics, Genomics, Proteomics and Informatics. Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6754-9_14713.
Full text
8
Saxena, Shipra, Sneha Yogindran, Manmohan Arya, Yogita Sharma, and Chandra Pal Singh. "RNAi-Mediated Control of Lepidopteran Pests of Important Crop Plants." In Moths and Caterpillars. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.96429.
Full textAbstract:
Insects as pests destroy annually an estimated 18–20% of the crop production worldwide. Caterpillars, the larval stage of moths, are the major pests of agricultural products owing to their voracious feeding habits. In the past few decades, the potent methods of insect control, such as insecticides and Bt toxins, have been constrained as a result of health hazards, environmental issues, and development of resistance, after their prolonged application. Thus, there is need to find alternative options to improve plant protection strategies. Recently, RNA interference (RNAi), the post-transcriptional gene-silencing mechanism, has emerged as one of such a novel, sustainable, and environment friendly approaches for insect management and crop protection. RNAi technology relies on selection of a vital insect pest target gene and its expression as a double stranded RNA or stem-loop RNA molecule, which is recognized by the host RNAi machinery and processed into small interfering RNAs (siRNAs) or microRNAs (miRNAs). The siRNA/miRNA along with the RNA-induced silencing complex (RISC) binds to the complimentary mRNA and induce gene silencing at post-transcriptional level. With effective target-gene selection and transgenic plants expressing these precursor RNA molecules, insect pests of various crops have been efficiently managed. In this chapter, we discuss the basic mechanism of RNAi and its application in controlling lepidopteran pests of important crop plants.
9
Primrose, Sandy B. "A Virus That Promotes Its Own Transfer: Tomato Spotted Wilt Virus." In Microbiology of Infectious Disease. Oxford University Press, 2022. http://dx.doi.org/10.1093/oso/9780192863843.003.0024.
Full textAbstract:
Tomato spotted wilt virus (TSWV) is a persistent plant virus; that is, one that replicates in both its insect vector (thrips) and plants. The viral NSs protein interferes with the plant’s RNA-induced silencing complex that is the first line of defence against virus infection. The NSs protein also interferes with the plant’s jasmonate-signalling pathway and suppresses the formation of insect-repellent terpenes. This makes infected plants more attractive to thrips than uninfected plants. Infected plants also have a higher free amino acid content which favours thrips reproduction. TSWV adapts to new plant hosts by the selection of mutants in its NSs and NSm proteins, mutation being facilitated by the error-prone nature of RNA replication.
10
Zayani, Riham, Amira Ben Hassine, Amal Rabti, Amal Raouaf, and Noureddine Raouafi. "Electrochemical and Optical Detection of MicroRNAs as Biomarkers for Cancer Diagnosis." In Current Cancer Biomarkers. BENTHAM SCIENCE PUBLISHERS, 2023. http://dx.doi.org/10.2174/9789815079364123010016.
Full textAbstract:
According to the miRBase (v 22.1), released on October 2018, there are more than 1900 identified human microRNA mature sequences. MicroRNAs (aka miRNAs or miRs) are a class of short non-coding RNA sequences, which have been detected within the cells or in body fluids. They act as gene expression regulators and intervene in numerous physiologic and development processes. They post-transcriptionally/translationally regulate expression of some proteins by forming miRNA-induced silencing complex (mRISC) by binding to 3’-UTR regions of the target messenger RNA to inhibit the protein synthesis. It has been noted that up- and down-regulation of miRs are associated with the pathogenesis of several types of human cancers since their target proteins are tumor-suppressive or oncogenic ones. This chapter will present a general summary of miRNA biogenesis, their link to cancer, and biological methods for their detection. Thanks to their ease of use and high sensitivity, electrochemical and optical techniques were used to detect miRNAs with or without the assistance of amplification methods. We will review the state-of-the-art electrochemical and optical methods for their detection, emphasizing the progress achieved in the last five years (2015-2020). Finally, we will present the main advantages, challenges, and future prospects for future research on detecting miRNAs for clinical diagnosis or prognosis in cancers.
Conference papers on the topic "RNA-induced silencing complex (RISC)"
1
Santhekadur, Prasanna K., Byoung Kwon Yoo, Rachel Gredler, et al. "Abstract 4706: Overexpression of the components of RNA-induced silencing complex: Contribution to hepatocellular carcinoma." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-4706.
Full textReports on the topic "RNA-induced silencing complex (RISC)"
1
Wang, X. F., and M. Schuldiner. Systems biology approaches to dissect virus-host interactions to develop crops with broad-spectrum virus resistance. United States-Israel Binational Agricultural Research and Development Fund, 2020. http://dx.doi.org/10.32747/2020.8134163.bard.
Full textAbstract:
More than 60% of plant viruses are positive-strand RNA viruses that cause billion-dollar losses annually and pose a major threat to stable agricultural production, including cucumber mosaic virus (CMV) that infects numerous vegetables and ornamental trees. A highly conserved feature among these viruses is that they form viral replication complexes (VRCs) to multiply their genomes by hijacking host proteins and remodeling host intracellular membranes. As a conserved and indispensable process, VRC assembly also represents an excellent target for the development of antiviral strategies that can be used to control a wide-range of viruses. Using CMV and a model virus, brome mosaic virus (BMV), and relying on genomic tools and tailor-made large-scale resources specific for the project, our original objectives were to: 1) Identify host proteins that are required for viral replication complex assembly. 2) Dissect host requirements that determine viral host range. 3) Provide proof-of-concept evidence of a viral control strategy by blocking the viral replication complex-localized phospholipid synthesis. We expect to provide new ways and new concepts to control multiple viruses by targeting a conserved feature among positive-strand RNA viruses based on our results. Our work is going according to the expected timeline and we are progressing well on all aims. For Objective 1, among ~6,000 yeast genes, we have identified 96 hits that were possibly play critical roles in viral replication. These hits are involved in cellular pathways of 1) Phospholipid synthesis; 2) Membrane-shaping; 3) Sterol synthesis and transport; 4) Protein transport; 5) Protein modification, among many others. We are pursuing several genes involved in lipid metabolism and transport because cellular membranes are primarily composed of lipids and lipid compositional changes affect VRC formation and functions. For Objective 2, we have found that CPR5 proteins from monocotyledon plants promoted BMV replication while those from dicotyledon plants inhibited it, providing direct evidence that CPR5 protein determines the host range of BMV. We are currently examining the mechanisms by which dicot CPR5 genes inhibit BMV replication and expressing the dicot CPR5 genes in monocot plants to control BMV infection. For Objective 3, we have demonstrated that substitutions in a host gene involved in lipid synthesis, CHO2, prevented the VRC formation by directing BMV replication protein 1a (BMV 1a), which remodels the nuclear membrane to form VRCs, away from the nuclear membrane, and thus, no VRCs were formed. This has been reported in Journal of Biological Chemistry. Based on the results from Objective 3, we have extended our plan to demonstrate that an amphipathic alpha-helix in BMV 1a is necessary and sufficient to target BMV 1a to the nuclear membrane. We further found that the counterparts of the BMV 1a helix from a group of viruses in the alphavirus-like superfamily, such as CMV, hepatitis E virus, and Rubella virus, are sufficient to target VRCs to the designated membranes, revealing a conserved feature among the superfamily. A joint manuscript describing these exciting results and authored by the two labs will be submitted shortly. We have also successfully set up systems in tomato plants: 1) to efficiently knock down gene expression via virus-induced gene silencing so we could test effects of lacking a host gene(s) on CMV replication; 2) to overexpress any gene transiently from a mild virus (potato virus X) so we could test effects of the overexpressed gene(s) on CMV replication. In summary, we have made promising progress in all three Objectives. We have identified multiple new host proteins that are involved in VRC formation and may serve as good targets to develop antiviral strategies; have confirmed that CPR5 from dicot plants inhibited viral infection and are generating BMV-resistance rice and wheat crops by overexpressing dicot CPR5 genes; have demonstrated to block viral replication by preventing viral replication protein from targeting to the designated organelle membranes for the VRC formation and this concept can be further employed for virus control. We are grateful to BARD funding and are excited to carry on this project in collaboration.