Relevant bibliographies by topics / Modifications of tRNA

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Academic literature on the topic 'Modifications of tRNA'

Author: Grafiati
Published: 9 March 2023

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Journal articles on the topic "Modifications of tRNA"

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Huber, Sabrina, Andrea Leonardi, Peter Dedon, and Thomas Begley. "The Versatile Roles of the tRNA Epitranscriptome during Cellular Responses to Toxic Exposures and Environmental Stress." Toxics 7, no. 1 (March 25, 2019): 17. http://dx.doi.org/10.3390/toxics7010017.

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Living organisms respond to environmental changes and xenobiotic exposures by regulating gene expression. While heat shock, unfolded protein, and DNA damage stress responses are well-studied at the levels of the transcriptome and proteome, tRNA-mediated mechanisms are only recently emerging as important modulators of cellular stress responses. Regulation of the stress response by tRNA shows a high functional diversity, ranging from the control of tRNA maturation and translation initiation, to translational enhancement through modification-mediated codon-biased translation of mRNAs encoding stress response proteins, and translational repression by stress-induced tRNA fragments. tRNAs need to be heavily modified post-transcriptionally for full activity, and it is becoming increasingly clear that many aspects of tRNA metabolism and function are regulated through the dynamic introduction and removal of modifications. This review will discuss the many ways that nucleoside modifications confer high functional diversity to tRNAs, with a focus on tRNA modification-mediated regulation of the eukaryotic response to environmental stress and toxicant exposures. Additionally, the potential applications of tRNA modification biology in the development of early biomarkers of pathology will be highlighted.
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Pereira, Marisa, Stephany Francisco, Ana Varanda, Mafalda Santos, Manuel Santos, and Ana Soares. "Impact of tRNA Modifications and tRNA-Modifying Enzymes on Proteostasis and Human Disease." International Journal of Molecular Sciences 19, no. 12 (November 24, 2018): 3738. http://dx.doi.org/10.3390/ijms19123738.

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Transfer RNAs (tRNAs) are key players of protein synthesis, as they decode the genetic information organized in mRNA codons, translating them into the code of 20 amino acids. To be fully active, tRNAs undergo extensive post-transcriptional modifications, catalyzed by different tRNA-modifying enzymes. Lack of these modifications increases the level of missense errors and affects codon decoding rate, contributing to protein aggregation with deleterious consequences to the cell. Recent works show that tRNA hypomodification and tRNA-modifying-enzyme deregulation occur in several diseases where proteostasis is affected, namely, neurodegenerative and metabolic diseases. In this review, we discuss the recent findings that correlate aberrant tRNA modification with proteostasis imbalances, in particular in neurological and metabolic disorders, and highlight the association between tRNAs, their modifying enzymes, translational decoding, and disease onset.
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Kazuhito, Tomizawa, and Fan-Yan Wei. "Posttranscriptional modifications in mitochondrial tRNA and its implication in mitochondrial translation and disease." Journal of Biochemistry 168, no. 5 (August 20, 2020): 435–44. http://dx.doi.org/10.1093/jb/mvaa098.

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Abstract A fundamental aspect of mitochondria is that they possess DNA and protein translation machinery. Mitochondrial DNA encodes 22 tRNAs that translate mitochondrial mRNAs to 13 polypeptides of respiratory complexes. Various chemical modifications have been identified in mitochondrial tRNAs via complex enzymatic processes. A growing body of evidence has demonstrated that these modifications are essential for translation by regulating tRNA stability, structure and mRNA binding, and can be dynamically regulated by the metabolic environment. Importantly, the hypomodification of mitochondrial tRNA due to pathogenic mutations in mitochondrial tRNA genes or nuclear genes encoding modifying enzymes can result in life-threatening mitochondrial diseases in humans. Thus, the mitochondrial tRNA modification is a fundamental mechanism underlying the tight regulation of mitochondrial translation and is essential for life. In this review, we focus on recent findings on the physiological roles of 5-taurinomethyl modification (herein referred as taurine modification) in mitochondrial tRNAs. We summarize the findings in human patients and animal models with a deficiency of taurine modifications and provide pathogenic links to mitochondrial diseases. We anticipate that this review will help understand the complexity of mitochondrial biology and disease.
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de Crécy-Lagard, Valérie, Robert L. Ross, Marshall Jaroch, Virginie Marchand, Christina Eisenhart, Damien Brégeon, Yuri Motorin, and Patrick A. Limbach. "Survey and Validation of tRNA Modifications and Their Corresponding Genes in Bacillus subtilis sp Subtilis Strain 168." Biomolecules 10, no. 7 (June 30, 2020): 977. http://dx.doi.org/10.3390/biom10070977.

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Extensive knowledge of both the nature and position of tRNA modifications in all cellular tRNAs has been limited to two bacteria, Escherichia coli and Mycoplasma capricolum. Bacillus subtilis sp subtilis strain 168 is the model Gram-positive bacteria and the list of the genes involved in tRNA modifications in this organism is far from complete. Mass spectrometry analysis of bulk tRNA extracted from B. subtilis, combined with next generation sequencing technologies and comparative genomic analyses, led to the identification of 41 tRNA modification genes with associated confidence scores. Many differences were found in this model Gram-positive bacteria when compared to E. coli. In general, B. subtilis tRNAs are less modified than those in E. coli, even if some modifications, such as m1A22 or ms2t6A, are only found in the model Gram-positive bacteria. Many examples of non-orthologous displacements and of variations in the most complex pathways are described. Paralog issues make uncertain direct annotation transfer from E. coli to B. subtilis based on homology only without further experimental validation. This difficulty was shown with the identification of the B. subtilis enzyme that introduces ψ at positions 31/32 of the tRNAs. This work presents the most up to date list of tRNA modification genes in B. subtilis, identifies the gaps in knowledge, and lays the foundation for further work to decipher the physiological role of tRNA modifications in this important model organism and other bacteria.
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Kimura, Satoshi, and Matthew K. Waldor. "The RNA degradosome promotes tRNA quality control through clearance of hypomodified tRNA." Proceedings of the National Academy of Sciences 116, no. 4 (January 8, 2019): 1394–403. http://dx.doi.org/10.1073/pnas.1814130116.

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The factors and mechanisms that govern tRNA stability in bacteria are not well understood. Here, we investigated the influence of posttranscriptional modification of bacterial tRNAs (tRNA modification) on tRNA stability. We focused on ThiI-generated 4-thiouridine (s4U), a modification found in bacterial and archaeal tRNAs. Comprehensive quantification ofVibrio choleraetRNAs revealed that the abundance of some tRNAs is decreased in a ΔthiIstrain in a stationary phase-specific manner. Multiple mechanisms, including rapid degradation of a subset of hypomodified tRNAs, account for the reduced abundance of tRNAs in the absence ofthiI. Through transposon insertion sequencing, we identified additional tRNA modifications that promote tRNA stability and bacterial viability. Genetic analysis of suppressor mutants as well as biochemical analyses revealed that rapid degradation of hypomodified tRNA is mediated by the RNA degradosome. Elongation factor Tu seems to compete with the RNA degradosome, protecting aminoacyl tRNAs from decay. Together, our observations describe a previously unrecognized bacterial tRNA quality control system in which hypomodification sensitizes tRNAs to decay mediated by the RNA degradosome.
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Galvanin, Adeline, Lea-Marie Vogt, Antonia Grober, Isabel Freund, Lilia Ayadi, Valerie Bourguignon-Igel, Larissa Bessler, et al. "Bacterial tRNA 2′-O-methylation is dynamically regulated under stress conditions and modulates innate immune response." Nucleic Acids Research 48, no. 22 (December 4, 2020): 12833–44. http://dx.doi.org/10.1093/nar/gkaa1123.

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Abstract RNA modifications are a well-recognized way of gene expression regulation at the post-transcriptional level. Despite the importance of this level of regulation, current knowledge on modulation of tRNA modification status in response to stress conditions is far from being complete. While it is widely accepted that tRNA modifications are rather dynamic, such variations are mostly assessed in terms of total tRNA, with only a few instances where changes could be traced to single isoacceptor species. Using Escherichia coli as a model system, we explored stress-induced modulation of 2′-O-methylations in tRNAs by RiboMethSeq. This analysis and orthogonal analytical measurements by LC-MS show substantial, but not uniform, increase of the Gm18 level in selected tRNAs under mild bacteriostatic antibiotic stress, while other Nm modifications remain relatively constant. The absence of Gm18 modification in tRNAs leads to moderate alterations in E. coli mRNA transcriptome, but does not affect polysomal association of mRNAs. Interestingly, the subset of motility/chemiotaxis genes is significantly overexpressed in ΔTrmH mutant, this corroborates with increased swarming motility of the mutant strain. The stress-induced increase of tRNA Gm18 level, in turn, reduced immunostimulation properties of bacterial tRNAs, which is concordant with the previous observation that Gm18 is a suppressor of Toll-like receptor 7 (TLR7)-mediated interferon release. This documents an effect of stress induced modulation of tRNA modification that acts outside protein translation.
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Strobel, M. C., and J. Abelson. "Effect of intron mutations on processing and function of Saccharomyces cerevisiae SUP53 tRNA in vitro and in vivo." Molecular and Cellular Biology 6, no. 7 (July 1986): 2663–73. http://dx.doi.org/10.1128/mcb.6.7.2663-2673.1986.

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The Saccharomyces cerevisiae leucine-inserting amber suppressor tRNA gene SUP53 (a tRNALeu3 allele) was used to investigate the relationship between precursor tRNA structure and mature tRNA function. This gene encodes a pre-tRNA which contains a 32-base intron. The mature tRNASUP53 contains a 5-methylcytosine modification of the anticodon wobble base. Mutations were made in the SUP53 intron. These mutant genes were transcribed in an S. cerevisiae nuclear extract preparation. In this extract, primary tRNA gene transcripts are end-processed and base modified after addition of cofactors. The base modifications made in vitro were examined, and the mutant pre-tRNAs were analyzed for their ability to serve as substrates for partially purified S. cerevisiae tRNA endonuclease and ligase. Finally, the suppressor function of these mutant tRNA genes was assayed after their integration into the S. cerevisiae genome. Mutant analysis showed that the totally intact precursor tRNA, rather than any specific sequence or structure of the intron, was necessary for efficient nonsense suppression by tRNASUP53. Less efficient suppressor activity correlated with the absence of the 5-methylcytosine modification. Most of the intron-altered precursor tRNAs were successfully spliced in vitro, indicating that modifications are not critical for recognition by the tRNA endonuclease and ligase.
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Strobel, M. C., and J. Abelson. "Effect of intron mutations on processing and function of Saccharomyces cerevisiae SUP53 tRNA in vitro and in vivo." Molecular and Cellular Biology 6, no. 7 (July 1986): 2663–73. http://dx.doi.org/10.1128/mcb.6.7.2663.

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The Saccharomyces cerevisiae leucine-inserting amber suppressor tRNA gene SUP53 (a tRNALeu3 allele) was used to investigate the relationship between precursor tRNA structure and mature tRNA function. This gene encodes a pre-tRNA which contains a 32-base intron. The mature tRNASUP53 contains a 5-methylcytosine modification of the anticodon wobble base. Mutations were made in the SUP53 intron. These mutant genes were transcribed in an S. cerevisiae nuclear extract preparation. In this extract, primary tRNA gene transcripts are end-processed and base modified after addition of cofactors. The base modifications made in vitro were examined, and the mutant pre-tRNAs were analyzed for their ability to serve as substrates for partially purified S. cerevisiae tRNA endonuclease and ligase. Finally, the suppressor function of these mutant tRNA genes was assayed after their integration into the S. cerevisiae genome. Mutant analysis showed that the totally intact precursor tRNA, rather than any specific sequence or structure of the intron, was necessary for efficient nonsense suppression by tRNASUP53. Less efficient suppressor activity correlated with the absence of the 5-methylcytosine modification. Most of the intron-altered precursor tRNAs were successfully spliced in vitro, indicating that modifications are not critical for recognition by the tRNA endonuclease and ligase.
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Pereira, Marisa, Diana R. Ribeiro, Miguel M. Pinheiro, Margarida Ferreira, Stefanie Kellner, and Ana R. Soares. "m5U54 tRNA Hypomodification by Lack of TRMT2A Drives the Generation of tRNA-Derived Small RNAs." International Journal of Molecular Sciences 22, no. 6 (March 14, 2021): 2941. http://dx.doi.org/10.3390/ijms22062941.

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Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recent evidence indicates that tsRNAs are also modified, however, the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. The tRNA methyltransferase TRMT2A catalyzes this modification, but its biological role remains mostly unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification and tsRNA formation. More specifically, m5U54 hypomodification is followed by overexpression of the ribonuclease angiogenin (ANG) that cleaves tRNAs near the anticodon, resulting in accumulation of 5′tRNA-derived stress-induced RNAs (5′tiRNAs), namely 5′tiRNA-GlyGCC and 5′tiRNA-GluCTC, among others. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tiRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tiRNA formation in mammalian cells. These results establish a link between tRNA hypomethylation and ANG-dependent tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.
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Lei, Lei, and Zachary Frome Burton. "“Superwobbling” and tRNA-34 Wobble and tRNA-37 Anticodon Loop Modifications in Evolution and Devolution of the Genetic Code." Life 12, no. 2 (February 8, 2022): 252. http://dx.doi.org/10.3390/life12020252.

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The genetic code evolved around the reading of the tRNA anticodon on the primitive ribosome, and tRNA-34 wobble and tRNA-37 modifications coevolved with the code. We posit that EF-Tu, the closing mechanism of the 30S ribosomal subunit, methylation of wobble U34 at the 5-carbon and suppression of wobbling at the tRNA-36 position were partly redundant and overlapping functions that coevolved to establish the code. The genetic code devolved in evolution of mitochondria to reduce the size of the tRNAome (all of the tRNAs of an organism or organelle). “Superwobbling” or four-way wobbling describes a major mechanism for shrinking the mitochondrial tRNAome. In superwobbling, unmodified wobble tRNA-U34 can recognize all four codon wobble bases (A, G, C and U), allowing a single unmodified tRNA-U34 to read a 4-codon box. During code evolution, to suppress superwobbling in 2-codon sectors, U34 modification by methylation at the 5-carbon position appears essential. As expected, at the base of code evolution, tRNA-37 modifications mostly related to the identity of the adjacent tRNA-36 base. TRNA-37 modifications help maintain the translation frame during elongation.
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Dissertations / Theses on the topic "Modifications of tRNA"

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Deogharia, Manisha. "PSEUDOURIDINE MODIFICATIONS IN HUMAN tRNAs AND ARCHAEAL rRNAs." OpenSIUC, 2018. https://opensiuc.lib.siu.edu/dissertations/1570.

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AN ABSTRACT OF THE DISSERTATION OF MANISHA DEOGHARIA, for the Doctor of Philosophy degree in Molecular Biology, Microbiology and Biochemistry presented on May 16, 2018, at Southern Illinois University, Carbondale TITLE: PSEUDOURIDINE MODIFICATIONS IN HUMAN tRNAs AND ARCHAEAL rRNAs MAJOR PROFESSOR: DR. RAMESH GUPTA RNAs undergo several post-transcriptional modifications inside the cell. The most abundant modification found in RNA is pseudouridine. Pseudouridine is present in all major classes of RNA. The classical TΨC sequence of tRNA reflects T (ribothymidine or 5-methyluridine) at position 54 in most Bacteria and Eukarya, and Ψ and C at positions 55 and 56, respectively, in nearly all tRNAs. TrmA and TruB homologs produce T54 and Ψ55, respectively, in Bacteria and Eukarya. However, archaeal tRNAs commonly have Ψ54 (or m1Ψ54) instead of T54, and Pus10 produces both Ψ54 and Ψ55 in these tRNAs. The pus10 gene is present in nearly all Archaea and most eukaryotes, but not in Bacteria and yeast. This coincides with the presence of Ψ54 in archaeal tRNAs and certain tRNAs (for Gln, Trp, Pro Thr, etc.) of animals, and its absence in the tRNAs of Bacteria and yeast. tRNAs for Trp and Pro that function as primers for replication of retroviruses also contain Ψ54. We found that Pus10 is the Ψ54 synthase in eukaryotes. The Ψ54 activity is specific for certain tRNAs, and it requires a conserved Am1AAU sequence at positions 57-60 of the tRNA for its maximum activity. Recombinant Pus10 can also form Ψ54 in select tRNAs and presence of m1A at position 58 is necessary for its maximum activity. Humans have two paralogs of TruB, TruB1, and TruB2 which are predicted to be the Ψ55 synthases for cytoplasmic and mitochondrial tRNAs, respectively. We found that recombinant human Pus10 can also modify Ψ55 of tRNAs in vitro. This Ψ55 activity of human Pus10 is not selective for specific tRNAs. Another pseudouridine synthase, Cbf5, which functions in guide dependent manner, is necessary for Ψ production in 23S rRNA of H. volcanii. Cbf5 is the catalytic component of the box H/ACA ribonucleoprotein complex that brings about these modifications. It consists of a guide RNA and three core proteins Nop10, Gar1, and L7Ae along with Cbf5. We found that Nop10 is necessary for Ψ production in 23S rRNA.
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Sun, Congliang. "Probing the UVA-induced effect on tRNA and tRNA modifications by LC-MS." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1573570369421344.

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Joardar, Archi. "GUIDE RNA-DEPENDENT AND INDEPENDENT tRNA MODIFICATIONS IN ARCHAEA." OpenSIUC, 2012. https://opensiuc.lib.siu.edu/dissertations/625.

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Stable RNAs undergo a wide variety of post-transcriptional modifications, that add to the functional repertoire of these molecules. Some of these modifications are catalyzed by stand-alone protein enzymes, while some others are catalyzed by RNA-protein complexes. tRNAs from all domains of life contain many such modifications, that increase their structural stability and refine their decoding properties. Certain regions of tRNAs are more frequently modified than others. Two such regions are the anticodon loop, and the TψC stem. In the halophilic euryarchaeon Haloferax volcanii, tRNATrp and tRNAMet, both of which are transcribed as intron-containing pre-tRNA forms, contain Cm34 and ψ54, in addition to other modifications, in these two regions, respectively. The Cm34 modification in both cases is RNP-mediated: tRNATrp Cm34 formation being guided by its own intron, while that of tRNAMet being guided by a unique guide RNA called sR-tMet. We created genomic deletion of H. volcanii tRNATrp intron by homologous recombination based technique, and showed that this strain is viable, and does not demonstrate any observable growth phenotype. However, the corresponding modifications are absent in this intron-deleted strain. Our structural and functional characterizations of sR-tMet revealed that it is unique in its structural properties and deviates considerably from its homologs in other Archaea. We also identified a novel L7Ae (a core protein associated with archaeal methylation guide RNPs) binding motif in sR-tMet. ψ54, the near universal modification found in TψC stem-loop of archaeal tRNAs is catalyzed by the protein Pus10. An earlier study from our laboratory had shown that Pus10 from two different archaea, Methanocaldococcus jannaschii (MjPus10) and Pyrococcus furiosus (PfuPus10) have differential activities towards ψ54 formation. Using the crystal structure of Human Pus10 as template, we created homology models of MjPus10 and PfuPus10 proteins and identified several residues and motifs that might lead to this difference in activity. By a combination of both in vitro and in vivo mutational approaches, we confirmed several previously unidentified residues/motifs that serve as positive determinants of tRNA ψ54 formation. Finally, as an extension to this study, we have identified a novel tRNA ψ54 forming activity in mammalian nuclear extracts, and attributed this activity to Pus10.
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Howell, Nathan W. "Substrate specificity of the Trm10 m1R9 tRNA methyltransferase family." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1563209805137069.

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Esberg, Anders. "Functional aspects of wobble uridine modifications in yeast tRNA." Doctoral thesis, Umeå : Department of Molecular Biology, Umeå Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1093.

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Lobue, Peter. "Towards the Parallel, Accurate, and High-throughput Mapping of RNA Modifications by Liquid Chromatography Tandem Mass Spectrometry." University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595005836099446.

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Rodríguez, Escribà Marta. "Role of tRNA modifications in the synthesis of the extracellular matrix." Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/668499.

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Transfer RNAs (tRNAs) are key adaptor molecules that mediate decoding of messenger RNAs (mRNAs) into proteins by complementary pairing of their anticodons with mRNA codons. tRNAs that undergo adenosine to inosine editing at the wobble base, or position 34, display expanded codon decoding capacity as inosine enables pairing not only with uridine, but also with cytosine and adenosine. The essential heterodimeric enzyme Adenosine Deaminase Acting on Transfer RNA (ADAT) catalyzes this post-transcriptional modification in eukaryotes and is comprised of subunits ADAT2 and ADAT3. Emergence of heterodimeric ADAT has been proposed to have shaped both tRNA gene content and codon composition of eukaryotic genomes in such a way that these two features became mirrored. Although the exact contribution of wobble inosine (I34) to translation elongation has not been established, previous reports have suggested that it might play a role in improving translational efficiency and accuracy of genes enriched in codons recognized by I34-modified tRNAs. To further understand the role of the inosine modification in translation, we generated cell lines depleted in the catalytic subunit ADAT2. Silencing of ADAT2 lead to impaired cellular proliferation and had a variable impact on the expression of genes coding for extracellular matrix (ECM) proteins such as mucins. Notably, ADAT2 deficiency did not have major effects on the post-translational glycosylation of mucins, neither did it trigger the unfolded protein response. Supported by the absence of clear defects in decoding rates in ADAT2 depleted cells, as measured by ribosome profiling, our findings suggest that a reduced pool of I34-modified tRNAs might suffice to carry out cellular functions in steady-state conditions. However, we found that, under circumstances involving a high demand for these tRNAs such as airway remodeling, ADAT2 is required for the proper translation of an ECM gene enriched in stretches of codons read by I34-tRNAs. Taken together, our results suggest that the inosine modification is particularly relevant for the synthesis of ECM proteins during specialized processes including neural development and airway remodeling. The importance of the inosine modification has been recently underscored by the identification of pathogenic mutations in the gene encoding ADAT3, all of which share common neurodevelopmental phenotypes. The most prevalent mutation identified to date is a valine to methionine (V144M) substitution that is linked to intellectual disability and strabismus. In the present study we characterized human ADAT in terms of activity and quaternary structure, and investigated the effect of the ADAT3 V144M mutation on the enzyme. We showed that the V144M substitution leads to decreased enzymatic activity of ADAT, which might result from alterations in the tertiary structure and subcellular localization of ADAT3 that were found to be associated to the mutation.
Els ARNs de transferència (ARNt) són molècules que tenen un paper clau en el procés de traducció dels ARN missatgers (ARNm) en proteïnes mitjançant la interacció del seu anticodó amb codons d’ARNm. Els ARNt que passen per un procés d’edició d’adenosina a inosina a la base wobble, o posició 34, són capaços de llegir més d’un codó d’ARNm gràcies a la capacitat de la inosina de reconèixer els tres nucleòtids uridina, citidina i adenosina. L’enzim responsable d’aquesta modificació post-transcripcional en eucariotes s’anomena Adenosina Deaminasa específica per l’ARNt (ADAT), es tracta d’un complex heterodimèric format per les subunitats ADAT2 i ADAT3 que és essencial per a la viabilitat de l’organisme. Estudis previs han proposat que l’aparició d’ADAT va determinar el nombre de còpies gèniques de cada ARNt així com la composició de codons presents als genomes eucariòtics de tal manera que aquests dos factors estiguessin mútuament balancejats. Tot i que la contribució precisa de la inosina 34 (I34) a la traducció de proteïnes durant la fase d’elongació encara s’ha determinat experimentalment, algunes investigacions han suggerit que podria jugar un rol en l’eficiència i fidelitat de traducció de gens enriquits en codons reconeguts per ARNt modificats amb I34. Amb l’objectiu d’investigar el rol de la inosina en la traducció, hem generat línies cel·lulars on el gen codificant per ADAT2 ha estat silenciat. La depleció d’ADAT2 comporta un retard en el creixement cel·lular i té un efecte variable en l’expressió gènica de proteïnes de la matriu extracel·lular. El patró de modificacions post-traduccionals de glicosilació d’aquestes proteïnes no resulta alterat per la deficiència d’ADAT2, que tampoc activa la resposta a proteïnes desplegades. Juntament amb l’absència de defectes en la velocitat d’elongació analitzada per ribosome profiling, aquestes observacions suggereixen que la cèl·lula és capaç de dur a terme les seves funcions amb un nombre reduït d’ARNt modificats amb inosina. Hem vist, però, que en condicions que requereixen majors quantitats d’ARNt inosinats, la depleció d’ADAT2 dóna lloc a la traducció ineficient d’un gen de matriu extracel·lular altament enriquit en codons sensibles llegits per ARNt modificats. Així doncs, els nostres resultats indiquen que la inosina pot exercir un rol important en la síntesi de proteïnes de la matriu extracel·lular, particularment durant processos de desenvolupament neuronal i de remodelat de les vies respiratòries. La rellevància de la modificació I34 s’ha vist reforçada recentment per la identificació de mutacions de caire patogènic localitzades al gen que codifica ADAT3. Totes elles tenen en comú la presència de fenotips relacionats amb el desenvolupament neurològic. La mutació d’ADAT3 més comuna consisteix en la substitució d’un residu valina per un metionina (V144M) i està associada a la manifestació de discapacitat intel·lectual i estrabisme. En el present estudi hem caracteritzat l’activitat enzimàtica i l’estructura quaternària de l’ADAT humà, així com l’impacte de la mutació V144M d’ADAT3 en el complex heterdimèric. Els nostres revelen que la substitució V144M dóna lloc a una menor activitat enzimàtica d’ADAT. És possible que aquesta reducció es vegi influïda per les alteracions en l’estructura terciària i en la localització cel·lular d’ADAT3 que indueix la mutació.
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Chatterjee, Kunal. "A TALE OF TWO METHYLATION MODIFICATIONS IN ARCHAEAL RNAs." OpenSIUC, 2014. https://opensiuc.lib.siu.edu/dissertations/806.

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In all the three domains of life, most RNAs undergo post transcriptional modifications both on the bases as well as the ribose sugars of the individual ribonucleotides. 2'-O-methylation of ribose sugars and isomerization of Uridines to Pseudouridines are two most predominant modifications in rRNAs and tRNAs across all domains of life. Besides 2'-O-methylation of ribose sugars, methylation of pseudouridine (Ø) at position 54 of tRNA, producing m1Ø, is a hallmark of many archaeal species but the specific methylase involved in the formation of this modification had yet to be characterized. A comparative genomics analysis had previously identified COG1901 (DUF358), part of the SPOUT superfamily, as a candidate for this missing methylase family. To test this prediction, the COG1901 encoding gene, HVO_1989, was deleted from the Haloferax volcanii genome. Analyses of modified base contents indicated that while m1Ø was present in tRNA extracted from the wild-type strain, it was absent from tRNA extracted from the mutant strain. Expression of the gene encoding COG1901 from Halobacterium sp. NRC-1, VNG1980C, complemented the m1Ø minus phenotype of the ÄHVO_1989 strain. This in vivo validation was extended with in vitro tests. Using the COG1901 recombinant enzyme from Methanocaldococcus jannaschii (Mj1640), purified enzyme Pus10 from M. jannaschii and full-size tRNA transcripts or TØ-arm (17-mer) fragments as substrates, the sequential pathway of m1Ø54 formation in Archaea was reconstituted. The methylation reaction is AdoMet-dependent. The efficiency of the methylase reaction depended on the identity of the residue at position 55 of the TØ-loop. The presence of Ø55 allowed the efficient conversion of Ø54 to m1Ø54, whereas in the presence of C55 the reaction was rather inefficient and no methylation reaction occurred if a purine was present at this position. These results led to renaming the Archaeal COG1901 members as TrmY proteins. Another aim of this study was to investigate the mechanism of target RNA recruitment to a box C/D sRNP. From data obtained, we have made the following hypothesis- aNop5p, either alone or as a heterodimer with Fibrillarin, binds to single stranded bulges and loops of target RNA. This aNop5p bound target is then hybridized to an assembling guide sRNP complex containing the guide RNA and L7Ae or guide RNA, L7Ae and aNop5p. If the guide:target sequences are complementary to each other, they hybridize and the target nucleotide gets modified. We also think that post modification, the guide and target strands separate, the core proteins rearrange themselves on the guide RNA and then prime the guide RNA for next round of modification. Compared to the general archaeal populations, haloarchaea contain significantly fewer number of box C/D guide RNAs. In archaea, previous studies have underscored the importance of a symmetric assembly of the core proteins on the sRNA. This meant that if the core proteins were unable to bind to either the terminal box C/D or the internal box C'/D' motifs, the sRNP was not efficient to carry out the modification of the target RNA. Essentially the only two haloarchaeal box C/D sRNPs known before had a symmetric architecture. In this study we discovered the first naturally occurring asymmetric box C/D sRNP called sR-41 in Haloferax volcannii. The architecture of Haloferax volcanii sR-41 box C/D sRNP seems to be closer in conformation to eukaryal snoRNPs (eukaryal counterparts of archaeal sRNPs) in which the core proteins assemble asymmetrically on the RNA. Till date, no information regarding the catalytic mechanism of an asymmetrically arranged eukaryal box C/D snoRNPs are available, because of unavailability of any assembly systems or crystal structures. Hence, this archaeal sR-41 guide sRNP provides a unique opportunity to study mechanism of modification in an asymmetrically arranged box C/D sRNP molecule.
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Matlock, Ashanti Ochumare. "Catalytic and Biological Implications of The Eukaryotic and Prokaryotic Thg1 Enzyme Family." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1555598687105069.

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Chen, Peng. "Function of wobble nucleoside modifications in tRNAs of Salmonella enterica Serovar Typhimurium." Doctoral thesis, Umeå universitet, Molekylärbiologi (Teknat- och Medfak), 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-328.

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Transfer RNA from all organisms has modified nucleosides and position 34 (the wobble position) is one of the most extensively modified positions. Some wobble nucleoside modifications restrict codon choice (e.g. 5-methylaminomethyl-2-thiouridine, mnm5s2U) while some extend the decoding capacity (e.g. uridine-5-oxyacetic acid, cmo5U). In this thesis the influence of wobble nucleoside modification on cell physiology and translation efficiency and accuracy is described. A mutant proL tRNA (proL207) was isolated that had an unmodified adenosine in the wobble position. Surprisingly, the proL207 mutant grows normally and is efficiently selected at the non-complementary CCC codon. The explanation of how an A34 containing tRNA can read CCC codon could be that a protonated A can form a base pair with C. cmo5U (uridine-5-oxyacetic acid) is present in the wobble position of five tRNA species in S.enterica. Two genes (cmoA and cmoB) have been identified that are involved in the synthetic pathway of cmo5U. Mutants were constructed in alanine, valine, proline, and threonine codon boxes which left only a cmo5U containing tRNA present in the cell. The influence of cmo5U on growth or on A site selection rates of the ternary complex was found to be tRNA dependent. During the study of the frameshift suppressor sufY of the hisC3737 frameshift mutation, a dominant mutation was found in YbbB protein, a selenouridine synthetase. The frameshifting occurs at CCC-CAA codon contexts and is specific for CAA codons, which are read by tRNAGlncmnm5s2UUG . The sufY204 mutation is a dominant mutation resulting in a change from Gly67 to Glu67 in the YbbB protein, and mediates the synthesis of several novel modified nucleosides/nucleotides (UKs) with unknown structure. The synthesis of these UKs is connected to the synthesis of cmnm5s2U34. The presence of UK on tRNAGlnU*UG reduced aminoacylation and therefore might account for the slow entry at CAA codons which could result in +1 frameshifting by P site tRNA. The selenourdine synthetase activity is not required for the synthesis of UKs. We hypothesize that an intrinsic activity that is low in the wild type protein has been elevated by the single amino acid substitution and results in the synthesis of UKs.
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Book chapters on the topic "Modifications of tRNA"

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Lyons, Shawn M., Marta M. Fay, and Pavel Ivanov. "Regulated tRNA Cleavage in Biology and Medicine: Roles of tRNA Modifications." In Modified Nucleic Acids in Biology and Medicine, 27–54. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-34175-0_2.

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Suzuki, Tsutomu. "Biosynthesis and function of tRNA wobble modifications." In Fine-Tuning of RNA Functions by Modification and Editing, 23–69. Berlin, Heidelberg: Springer Berlin Heidelberg, 2005. http://dx.doi.org/10.1007/b106361.

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Shigi, Naoki. "Sulfur Modifications in tRNA: Function and Implications for Human Disease." In Modified Nucleic Acids in Biology and Medicine, 55–71. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-34175-0_3.

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Edwards, Ashley M., Maame A. Addo, and Patricia C. Dos Santos. "tRNA Modifications as a Readout of S and Fe-S Metabolism." In Methods in Molecular Biology, 137–54. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1605-5_8.

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Antoine, Laura, and Philippe Wolff. "Mapping of Posttranscriptional tRNA Modifications by Two-Dimensional Gel Electrophoresis Mass Spectrometry." In Methods in Molecular Biology, 101–10. New York, NY: Springer US, 2020. http://dx.doi.org/10.1007/978-1-0716-0278-2_8.

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Kersten, H. "The Role of Coenzymes and tRNA Modifications in Metabolic Control of Gene Expression." In Biological Methylation and Drug Design, 163–74. Totowa, NJ: Humana Press, 1986. http://dx.doi.org/10.1007/978-1-4612-5012-8_14.

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Price, David H., and Michael W. Gray. "Editing of tRNA." In Modification and Editing of RNA, 289–305. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555818296.ch16.

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Auffinger, Pascal, and Eric Westhof. "Location and Distribution of Modified Nucleotides in tRNA." In Modification and Editing of RNA, 569–76. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555818296.app5.

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Romier, Christophe, Ralf Ficner, and Dietrich Suck. "Structural Basis of Base Exchange by tRNA-Guanine Transglycosylases." In Modification and Editing of RNA, 169–82. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555818296.ch9.

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Rubio, Mary Anne T., and Juan D. Alfonzo. "tRNA Modification, Editing, and Import in Mitochondria." In Organelle Genetics, 359–80. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-22380-8_14.

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Conference papers on the topic "Modifications of tRNA"

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Kurimoto, Ryota, Hiroki Tsutsumi, Saki Ikeuchi, and Hiroshi Asahara. "Abstract 2370: Tumor suppression potential of tRNA modification enzyme TruBs via let-7." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-2370.

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Haining, Liu, Zeng Xuezhen, Ren Xuxin, Kuang Ming, and Lin Shuibin. "IDDF2022-ABS-0068 Targeting tumor-intrinsic N7-methylguanosine tRNA modification inhibits MDSC recruitment and improves anti-PD-1 efficacy." In Abstracts of the International Digestive Disease Forum (IDDF), Hong Kong, 2–4 September 2022. BMJ Publishing Group Ltd and British Society of Gastroenterology, 2022. http://dx.doi.org/10.1136/gutjnl-2022-iddf.7.

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Bonham-Carter, Oliver, Ishwor Thapa, and Dhundy Bastola. "Evidence of post translational modification bias extracted from the tRNA and corresponding amino acid interplay across a set of diverse organisms." In BCB '14: ACM-BCB '14. New York, NY, USA: ACM, 2014. http://dx.doi.org/10.1145/2649387.2660848.

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Mininni, Mariavaleria, Luigi Guastamacchia, and Teresa Pagnelli. "Rinaturalizzare/reinventare/riparare: azioni paesaggistiche per il riuso del paesaggio estrattivo: il caso studio della nuova provincia BAT." In International Conference Virtual City and Territory. Roma: Centre de Política de Sòl i Valoracions, 2014. http://dx.doi.org/10.5821/ctv.8021.

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L’attività estrattiva ha costituito per la Puglia un importante motore di sviluppo economico e produttivo, uso del territorio legato alla sua tradizione storico-costruttiva. In particolare il bacino estrattivo della nuova provincia Barletta – Andria – Trani (BAT), a nord di Bari, in crisi ed in parte dismesso, è stato per la Regione uno dei riferimenti per l’ economia, non sempre sensibile verso le indotte trasformazioni sul paesaggio e territorio. Il presente contributo si propone di indagare quale possa essere il punto d’incontro tra il processo di pianificazione e quello produttivo, al fine di individuare strategie con cui operare il ripristino e la restituzione di usi, significati e valori a siti estrattivi ormai dismessi; attivando proattivamente e propositivamente processi virtuosi capaci di innescare da un lato una migliore gestione del paesaggio e dall’altro la necessaria innovazione nel sistema di gestione del comparto estrattivo risorse per il territorio. Partendo dall’atto di avvio del PTCP (Piano Territoriale di Coordinamento Provinciale), attento al recupero di cave esaurite ed abbandonate, si è cercato di definire un percorso metodologico e progettuale, nel quale il presupposto di riacquisire le cave esaurite in un processo di sviluppo sostenibile del territorio trova, attraverso azioni di paesaggio ripensate come le “3R”: Rinaturalizzare, Reinventare, Riparare, proposte strategiche di trasformazione territoriale in grado di delineare scenari futuri per il territorio e per i nuovi contesti di vita. Operativamente attraverso lo strumento delle linee guida sono state messe a sistema le tre azioni di paesaggio in risposta alle criticità che derivano dai processi e conflitti in atto individuati dai progetti territoriali di paesaggio regionale, con l’obiettivo di pensare al riuso delle cave esaurite per consolidare e valorizzare i caratteri di ciascun contesto di vita, e creare nuovi valori e risignificazione dei luoghi. The mining activity has been an important driver of economic and productive development for the Apulia region, representing a land use inextricably linked to its historical and constituting tradition. In particular, the mining basin of the comprehensive province Barletta - Andria - Trani (BAT), north of Bari, is now undergoing a crisis and has been partly dismissed. However, it has always been an important driving force for the local economy of the region. The consequent problems associated with landscape modification and alteration, land use,waste and sludge proper disposal have never been sufficiently taken into account This paper aims to investigate a possible meeting point between the planning and the production processes, in order to identify recovery and recycling strategies, as well as identifying how to return the dismissed extraction sites their former uses, meanings and values by proactively activating virtuous processes capable of triggering a better landscape management on the one hand and, on the other hand, the necessary innovation of the mining management system, allowing it to be a territorial resource again. Starting from the act of initiating the PTCP (Provincial Territorial Coordination Plan), attentive to the recovery of exhausted quarries and abandoned, we have tried to define a methodological and design, in which the assumption of regaining the exhausted quarries in the process of development sustainable land is, through actions of landscape rethought as the "3R" renaturalise, Reinvent, Repairing, policy proposals of territorial transformation can outline future scenarios for the region and for new life contexts. Operationally, through the instrument of the guidelines have been put in the system landscape of three actions in response to the issues that arise from the processes and ongoing conflicts as identified by the local projects of regional landscape, with the aim of thinking about the reuse of exhausted quarries for consolidate and enhance the characteristics of each context of life, and create new values and re-signification of places.
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Reports on the topic "Modifications of tRNA"

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Deutsch, Christopher. Discovery and Characterization of the Proteins Involved in the Synthesis of N⁶-Threonylcarbamoyl Adenosine, a Nucleoside Modification of tRNA. Portland State University Library, January 2000. http://dx.doi.org/10.15760/etd.3075.

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