Academic literature on the topic 'MRNA Cleavage and Polyadenylation Factors'
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Journal articles on the topic "MRNA Cleavage and Polyadenylation Factors"
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MacDonald, C. C., J. Wilusz, and T. Shenk. "The 64-kilodalton subunit of the CstF polyadenylation factor binds to pre-mRNAs downstream of the cleavage site and influences cleavage site location." Molecular and Cellular Biology 14, no. 10 (October 1994): 6647–54. http://dx.doi.org/10.1128/mcb.14.10.6647-6654.1994.
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The CstF polyadenylation factor is a multisubunit complex required for efficient cleavage and polyadenylation of pre-mRNAs. Using an RNase H-mediated mapping technique, we show that the 64-kDa subunit of CstF can be photo cross-linked to pre-mRNAs at U-rich regions located downstream of the cleavage site of the simian virus 40 late and adenovirus L3 pre-mRNAs. This positional specificity of cross-linking is a consequence of CstF interaction with the polyadenylation complex, since the 64-kDa protein by itself is cross-linked at multiple positions on a pre-mRNA template. During polyadenylation, four consecutive U residues can substitute for the native downstream U-rich sequence on the simian virus 40 pre-mRNA, mediating efficient 64-kDa protein cross-linking at the downstream position. Furthermore, the position of the U stretch not only enables the 64-kDa polypeptide to be cross-linked to the pre-mRNA but also influences the site of cleavage. A search of the GenBank database revealed that a substantial portion of mammalian polyadenylation sites carried four or more consecutive U residues positioned so that they should function as sites for interaction with the 64-kDa protein downstream of the cleavage site. Our results indicate that the polyadenylation machinery physically spans the cleavage site, directing cleavage factors to a position located between the upstream AAUAAA motif, where the cleavage and polyadenylation specificity factor is thought to interact, and the downstream U-rich binding site for the 64-kDa subunit of CstF.
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MacDonald, C. C., J. Wilusz, and T. Shenk. "The 64-kilodalton subunit of the CstF polyadenylation factor binds to pre-mRNAs downstream of the cleavage site and influences cleavage site location." Molecular and Cellular Biology 14, no. 10 (October 1994): 6647–54. http://dx.doi.org/10.1128/mcb.14.10.6647.
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The CstF polyadenylation factor is a multisubunit complex required for efficient cleavage and polyadenylation of pre-mRNAs. Using an RNase H-mediated mapping technique, we show that the 64-kDa subunit of CstF can be photo cross-linked to pre-mRNAs at U-rich regions located downstream of the cleavage site of the simian virus 40 late and adenovirus L3 pre-mRNAs. This positional specificity of cross-linking is a consequence of CstF interaction with the polyadenylation complex, since the 64-kDa protein by itself is cross-linked at multiple positions on a pre-mRNA template. During polyadenylation, four consecutive U residues can substitute for the native downstream U-rich sequence on the simian virus 40 pre-mRNA, mediating efficient 64-kDa protein cross-linking at the downstream position. Furthermore, the position of the U stretch not only enables the 64-kDa polypeptide to be cross-linked to the pre-mRNA but also influences the site of cleavage. A search of the GenBank database revealed that a substantial portion of mammalian polyadenylation sites carried four or more consecutive U residues positioned so that they should function as sites for interaction with the 64-kDa protein downstream of the cleavage site. Our results indicate that the polyadenylation machinery physically spans the cleavage site, directing cleavage factors to a position located between the upstream AAUAAA motif, where the cleavage and polyadenylation specificity factor is thought to interact, and the downstream U-rich binding site for the 64-kDa subunit of CstF.
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Mangus, David A., Mandy M. Smith, Jennifer M. McSweeney, and Allan Jacobson. "Identification of Factors Regulating Poly(A) Tail Synthesis and Maturation." Molecular and Cellular Biology 24, no. 10 (May 15, 2004): 4196–206. http://dx.doi.org/10.1128/mcb.24.10.4196-4206.2004.
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ABSTRACT Posttranscriptional maturation of the 3′ end of eukaryotic pre-mRNAs occurs as a three-step pathway involving site-specific cleavage, polymerization of a poly(A) tail, and trimming of the newly synthesized tail to its mature length. While most of the factors essential for catalyzing these reactions have been identified, those that regulate them remain to be characterized. Previously, we demonstrated that the yeast protein Pbp1p associates with poly(A)-binding protein (Pab1p) and controls the extent of mRNA polyadenylation. To further elucidate the function of Pbp1p, we conducted a two-hybrid screen to identify factors with which it interacts. Five genes encoding putative Pbp1p-interacting proteins were identified, including (i) FIR1/PIP1 and UFD1/PIP3, genes encoding factors previously implicated in mRNA 3′-end processing; (ii) PBP1 itself, confirming directed two-hybrid results and suggesting that Pbp1p can multimerize; (iii) DIG1, encoding a mitogen-activated protein kinase-associated protein; and (iv) PBP4 (YDL053C), a previously uncharacterized gene. In vitro polyadenylation reactions utilizing extracts derived from fir1Δ and pbp1Δ cells and from cells lacking the Fir1p interactor, Ref2p, demonstrated that Pbp1p, Fir1p, and Ref2p are all required for the formation of a normal-length poly(A) tail on precleaved CYC1 pre-mRNA. Kinetic analyses of the respective polyadenylation reactions indicated that Pbp1p is a negative regulator of poly(A) nuclease (PAN) activity and that Fir1p and Ref2p are, respectively, a positive regulator and a negative regulator of poly(A) synthesis. We suggest a model in which these three factors and Ufd1p are part of a regulatory complex that exploits Pab1p to link cleavage and polyadenylation factors of CFIA and CFIB (cleavage factors IA and IB) to the polyadenylation factors of CPF (cleavage and polyadenylation factor).
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Chen, J., and C. Moore. "Separation of factors required for cleavage and polyadenylation of yeast pre-mRNA." Molecular and Cellular Biology 12, no. 8 (August 1992): 3470–81. http://dx.doi.org/10.1128/mcb.12.8.3470-3481.1992.
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Cleavage and polyadenylation of yeast precursor RNA require at least four functionally distinct factors (cleavage factor I [CF I], CF II, polyadenylation factor I [PF I], and poly(A) polymerase [PAP]) obtained from yeast whole cell extract. Cleavage of precursor occurs upon combination of the CF I and CF II fractions. The cleavage reaction proceeds in the absence of PAP or PF I. The cleavage factors exhibit low but detectable activity without exogenous ATP but are stimulated when this cofactor is included in the reaction. Cleavage by CF I and CF II is dependent on the presence of a (UA)6 sequence upstream of the GAL7 poly(A) site. The factors will also efficiently cleave precursor with the CYC1 poly(A) site. This RNA does not contain a UA repeat, and processing at this site is thought to be directed by a UAG...UAUGUA-type motif. Specific polyadenylation of a precleaved GAL7 RNA requires CF I, PF I, and a crude fraction containing PAP activity. The PAP fraction can be replaced by recombinant PAP, indicating that this enzyme is the only factor in this fraction needed for the reconstituted reaction. The poly(A) addition step is also dependent on the UA repeat. Since CF I is the only factor necessary for both cleavage and poly(A) addition, it is likely that this fraction contains a component which recognizes processing signals located upstream of the poly(A) site. The initial separation of processing factors in yeast cells suggests both interesting differences from and similarities to the mammalian system.
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Chen, J., and C. Moore. "Separation of factors required for cleavage and polyadenylation of yeast pre-mRNA." Molecular and Cellular Biology 12, no. 8 (August 1992): 3470–81. http://dx.doi.org/10.1128/mcb.12.8.3470.
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Cleavage and polyadenylation of yeast precursor RNA require at least four functionally distinct factors (cleavage factor I [CF I], CF II, polyadenylation factor I [PF I], and poly(A) polymerase [PAP]) obtained from yeast whole cell extract. Cleavage of precursor occurs upon combination of the CF I and CF II fractions. The cleavage reaction proceeds in the absence of PAP or PF I. The cleavage factors exhibit low but detectable activity without exogenous ATP but are stimulated when this cofactor is included in the reaction. Cleavage by CF I and CF II is dependent on the presence of a (UA)6 sequence upstream of the GAL7 poly(A) site. The factors will also efficiently cleave precursor with the CYC1 poly(A) site. This RNA does not contain a UA repeat, and processing at this site is thought to be directed by a UAG...UAUGUA-type motif. Specific polyadenylation of a precleaved GAL7 RNA requires CF I, PF I, and a crude fraction containing PAP activity. The PAP fraction can be replaced by recombinant PAP, indicating that this enzyme is the only factor in this fraction needed for the reconstituted reaction. The poly(A) addition step is also dependent on the UA repeat. Since CF I is the only factor necessary for both cleavage and poly(A) addition, it is likely that this fraction contains a component which recognizes processing signals located upstream of the poly(A) site. The initial separation of processing factors in yeast cells suggests both interesting differences from and similarities to the mammalian system.
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Zhao, Jing, Linda Hyman, and Claire Moore. "Formation of mRNA 3′ Ends in Eukaryotes: Mechanism, Regulation, and Interrelationships with Other Steps in mRNA Synthesis." Microbiology and Molecular Biology Reviews 63, no. 2 (June 1, 1999): 405–45. http://dx.doi.org/10.1128/mmbr.63.2.405-445.1999.
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SUMMARY Formation of mRNA 3′ ends in eukaryotes requires the interaction of transacting factors with cis-acting signal elements on the RNA precursor by two distinct mechanisms, one for the cleavage of most replication-dependent histone transcripts and the other for cleavage and polyadenylation of the majority of eukaryotic mRNAs. Most of the basic factors have now been identified, as well as some of the key protein-protein and RNA-protein interactions. This processing can be regulated by changing the levels or activity of basic factors or by using activators and repressors, many of which are components of the splicing machinery. These regulatory mechanisms act during differentiation, progression through the cell cycle, or viral infections. Recent findings suggest that the association of cleavage/polyadenylation factors with the transcriptional complex via the carboxyl-terminal domain of the RNA polymerase II (Pol II) large subunit is the means by which the cell restricts polyadenylation to Pol II transcripts. The processing of 3′ ends is also important for transcription termination downstream of cleavage sites and for assembly of an export-competent mRNA. The progress of the last few years points to a remarkable coordination and cooperativity in the steps leading to the appearance of translatable mRNA in the cytoplasm.
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Ryner, L. C., Y. Takagaki, and J. L. Manley. "Sequences downstream of AAUAAA signals affect pre-mRNA cleavage and polyadenylation in vitro both directly and indirectly." Molecular and Cellular Biology 9, no. 4 (April 1989): 1759–71. http://dx.doi.org/10.1128/mcb.9.4.1759-1771.1989.
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To investigate the role of sequences lying downstream of the conserved AAUAAA hexanucleotide in pre-mRNA cleavage and polyadenylation, deletions or substitutions were constructed in polyadenylation signals from simian virus 40 and adenovirus, and their effects were assayed in both crude and fractionated HeLa cell nuclear extracts. As expected, these sequences influenced the efficiency of both cleavage and polyadenylation as well as the accuracy of the cleavage reaction. Sequences near or upstream of the actual site of poly(A) addition appeared to specify a unique cleavage site, since their deletion resulted, in some cases, in heterogeneous cleavage. Furthermore, the sequences that allowed the simian virus 40 late pre-RNA to be cleaved preferentially by partially purified cleavage activity were also those at the cleavage site itself. Interestingly, sequences downstream of the cleavage site interacted with factors not directly involved in catalyzing cleavage and polyadenylation, since the effects of deletions were substantially diminished when partially purified components were used in assays. In addition, these sequences contained elements that could affect 3'-end formation both positively and negatively.
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Ryner, L. C., Y. Takagaki, and J. L. Manley. "Sequences downstream of AAUAAA signals affect pre-mRNA cleavage and polyadenylation in vitro both directly and indirectly." Molecular and Cellular Biology 9, no. 4 (April 1989): 1759–71. http://dx.doi.org/10.1128/mcb.9.4.1759.
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To investigate the role of sequences lying downstream of the conserved AAUAAA hexanucleotide in pre-mRNA cleavage and polyadenylation, deletions or substitutions were constructed in polyadenylation signals from simian virus 40 and adenovirus, and their effects were assayed in both crude and fractionated HeLa cell nuclear extracts. As expected, these sequences influenced the efficiency of both cleavage and polyadenylation as well as the accuracy of the cleavage reaction. Sequences near or upstream of the actual site of poly(A) addition appeared to specify a unique cleavage site, since their deletion resulted, in some cases, in heterogeneous cleavage. Furthermore, the sequences that allowed the simian virus 40 late pre-RNA to be cleaved preferentially by partially purified cleavage activity were also those at the cleavage site itself. Interestingly, sequences downstream of the cleavage site interacted with factors not directly involved in catalyzing cleavage and polyadenylation, since the effects of deletions were substantially diminished when partially purified components were used in assays. In addition, these sequences contained elements that could affect 3'-end formation both positively and negatively.
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Morlando, Mariangela, Paolo Greco, Bernhard Dichtl, Alessandro Fatica, Walter Keller, and Irene Bozzoni. "Functional Analysis of Yeast snoRNA and snRNA 3′-End Formation Mediated by Uncoupling of Cleavage and Polyadenylation." Molecular and Cellular Biology 22, no. 5 (March 1, 2002): 1379–89. http://dx.doi.org/10.1128/mcb.22.5.1379-1389.2002.
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ABSTRACT Many nuclear and nucleolar small RNAs are accumulated as nonpolyadenylated species and require 3′-end processing for maturation. Here, we show that several genes coding for box C/D and H/ACA snoRNAs and for the U5 and U2 snRNAs contain sequences in their 3′ portions which direct cleavage of primary transcripts without being polyadenylated. Genetic analysis of yeasts with mutations in different components of the pre-mRNA cleavage and polyadenylation machinery suggests that this mechanism of 3"-end formation requires cleavage factor IA (CF IA) but not cleavage and polyadenylation factor activity. However, in vitro results indicate that other factors participate in the reaction besides CF IA. Sequence analysis of snoRNA genes indicated that they contain conserved motifs in their 3" noncoding regions, and mutational studies demonstrated their essential role in 3"-end formation. We propose a model in which CF IA functions in cleavage and polyadenylation of pre-mRNAs and, in combination with a different set of factors, in 3"-end formation of nonpolyadenylated polymerase II transcripts.
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McCracken, Susan, Mark Lambermon, and Benjamin J. Blencowe. "SRm160 Splicing Coactivator Promotes Transcript 3′-End Cleavage." Molecular and Cellular Biology 22, no. 1 (January 1, 2002): 148–60. http://dx.doi.org/10.1128/mcb.22.1.148-160.2002.
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ABSTRACT Individual steps in the processing of pre-mRNA, including 5′-end cap formation, splicing, and 3′-end processing (cleavage and polyadenylation) are highly integrated and can influence one another. In addition, prior splicing can influence downstream steps in gene expression, including export of mRNA from the nucleus. However, the factors and mechanisms coordinating these steps in the maturation of pre-mRNA transcripts are not well understood. In the present study we demonstrate that SRm160 (for serine/arginine repeat-related nuclear matrix protein of 160 kDa), a coactivator of constitutive and exon enhancer-dependent splicing, participates in 3′-end formation. Increased levels of SRm160 promoted the 3′-end cleavage of transcripts both in vivo and in vitro. Remarkably, at high levels in vivo SRm160 activated the 3′-end cleavage and cytoplasmic accumulation of unspliced pre-mRNAs, thereby uncoupling the requirement for splicing to promote the 3′-end formation and nuclear release of these transcripts. Consistent with a role in 3′-end formation coupled to splicing, SRm160 was found to associate specifically with the cleavage polyadenylation specificity factor and to stimulate the 3′-end cleavage of splicing-active pre-mRNAs more efficiently than that of splicing-inactive pre-mRNAs in vitro. The results provide evidence for a role for SRm160 in mRNA 3′-end formation and suggest that the level of this splicing coactivator is important for the proper coordination of pre-mRNA processing events.
Dissertations / Theses on the topic "MRNA Cleavage and Polyadenylation Factors"
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Oruganty, Aparna. "Role of the Cytoplasmic Polyadenylation Element Binding Proteins in Neuron: A Dissertation." eScholarship@UMMS, 2013. http://escholarship.umassmed.edu/gsbs_diss/648.
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Genome regulation is an extremely complex phenomenon. There are various mechanisms in place to ensure smooth performance of the organism. Post-transcriptional regulation of gene expression is one such mechanism. Many proteins bind to mRNAs and regulate their translation. In this thesis, I have focused on the Cytoplasmic Polyadenylation Element Binding family of proteins (CPEB1-4); a group of sequence specific RNA binding proteins important for cell cycle progression, senescence, neuronal function and plasticity. CPEB protein binds mRNAs containing a short Cytoplasmic Polyadenylation Element (CPE) in 3’ untranslated Region (UTR) and regulates the polyadenylation of these mRNAs and thereby controls translation. In Chapter II, I have presented my work on the regulation of mitochondrial function by CPEB. CPEB knockout mice have brain specific defects in mitochondrial function owing to a reduction in Electron transport chain complex I component protein NDUFV2. CPEB controls the translation of this NDUFV2 mRNA and thus affects mitochondrial function. A consequence of this reduced bioenergetics is reduced growth and branching of neurons, again emphasizing the importance of this pathway. Chapter III focuses on the role of CPEB4 in neuronal survival and protection against apoptosis. CPEB4 shuttles between nucleus and cytoplasm and becomes nuclear in response to stimulation with ionotropic glutamate receptors, focal ischemia in vivo and when cultured neurons are deprived of oxygen and glucose; nuclear CPEB4 affords protection against apoptosis in ischemia model. The underlying cause for nuclear translocation is reduction in Endoplasmic Reticulum calcium levels. These studies give an insight into the function and dynamics of these two RNA binding proteins and provide a better understanding of cellular biology.
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Hardy, Jessica. "Human cleavage factor I (CFIm) and its role in alternative polyadenylation of pre-mRNA." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:a3ba5d10-b3fa-4ab7-9709-a0d642e21543.
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For many human protein-coding genes, alternative cleavage and polyadenylation (APA) of pre-mRNA generates distinct 3' untranslated regions (3'UTRs) with differing regulatory potential. Widespread 3'UTR shortening via APA occurs in proliferative cell states, including cancer, where it can lead to oncogene overexpression. There has therefore been significant interest in identifying factors which influence poly(A) site choice in different physiological states. The multi-subunit human cleavage factor I complex (CFIm), a core component of the mammalian pre-mRNA cleavage machinery, has been identified as a potential master regulator of APA, as its depletion leads to widespread 3'UTR shortening. However, mechanistic understanding of how CFIm influences poly(A) site selection, and how its activity is regulated, is lacking. In this work, gene editing was used to generate cell lines with substantial, permanent depletion of the 25 kDa or 68 kDa subunits of CFIm (CFIm25 and CFIm68), which exhibited the expected 3'UTR shortening for representative transcripts. Reversal of this 3'UTR shortening by CFIm25 or CFIm68 re-expression provided the basis for a complementation assay, which allowed various aspects of CFIm25 and CFIm68 function to be investigated in vivo. The capacity of CFIm25 to recognise UGUA RNA sequences was shown to make an important contribution to poly(A) site selection transcriptome-wide, and a novel function for the C-terminal arginine/serine-rich (RS domain) of CFIm68 in poly(A) site selection was identified. The potential contribution of CFIm post-translational modification (PTM) to APA regulation was also explored. Novel acetylation sites on CFIm25 and CFIm68 were identified, as well as extensive serine phosphorylation in the CFIm68 RS domain. Complementation analysis revealed that phosphomimetic mutations in this RS domain inhibited distal poly(A) site selection, suggesting a potential role for CFIm68 phosphorylation in APA regulation. Taken together, the findings presented here provide insights into several important determinants of CFIm function, and the complementation assay developed provides a useful tool for future investigations.
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Bandyopadhyay, Amrita. "Analysis of the Arabidopsis Polyadenylation Factors PAP1, CstF64 and CstF77 and their characteristic inter-relationship." UKnowledge, 2009. http://uknowledge.uky.edu/gradschool_theses/601.
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3’-end modification by polyadenylation is a ubiquitous feature of almost all eukaryotic mRNA species and is catalyzed by a consortium of enzymes, the polyadenylation factors. Poly(A) polymerase (PAP), the enzyme catalyzing the addition of adenosine residues during the polyadenylation stage, exists in four isoforms within Arabidopsis. In silico and yeast two-hybrid studies showed that PAP1 has unique expression and interaction pattern in Arabidopsis, suggesting non-canonical functions of PAP1. Its exclusive interaction with PAP4 has not been reported in other living systems until now and hints at a difference in polyadenylation in plants with respect to mammals and yeast. Cleavage Stimulation Factor (CstF), a heterotrimeric complex of the polyadenylation factors CstF50, CstF64 and CstF77, plays a role largely in cleavage of pre-mRNA. This study highlights some aspects of the Arabidopsis homologs of CstF64 and CstF77, central to various cellular processes other than nuclear polyadenylation. In silico studies showed an elevated expression of CstF64 in the pollen while that of CstF77 remained fairly low. Yeast two-hybrid assays indicated a novel kind of interaction of CstF64 with Fip1(V). It is also speculated from sub-cellular localization techniques by agroinfiltration in tobacco leaves that CstF64 localizes in the cytoplasm and CstF77 in the nucleus, as found for the orthologs of CstF77 in other systems.
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Luo, Weifei. "The coupling of transcription termination by RNA polymerase II to MRNA 3' end processing in Saccharomyces cerevisiae /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2006.
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Thesis (Ph.D. in Biochemistry) -- University of Colorado at Denver and Health Sciences Center, 2006.Typescript. Includes bibliographical references (leaves 135-145). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;
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Burns, David M. "Post-Transcriptional Control of Human Cellular Senescence: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/491.
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The central dogma of biology asserts that DNA is transcribed into RNA and RNA is translated into protein. However, this overtly simplistic assertion fails to portray the highly orchestrated and regulated mechanisms of transcription and translation. During the process of transcription, RNA provides the template for translation and protein synthesis as well as the structural and sequence specificity of many RNA and protein-based machines. While only 1-5% of the genome will escape the nucleus to be translated as mRNAs, complex, parallel, highly-conserved mechanisms have evolved to regulate specific mRNAs. Trans-acting factors bind cis-elements in both the 5" and 3" untranslated regions of mRNA to regulate their stability, localization, and translation. While a few salient examples have been elucidated over the last few decades, mRNA translation can be reversibly regulated by the shortening and lengthening of the 3" polyadenylate tail of mRNA. CPEB, an important factor that nucleates a complex of proteins to regulate the polyadenylate tail of mRNA, exemplifies a major paradigm of translational control during oocyte maturation and early development. CPEB function is also conserved in neurons and somatic foreskin fibroblasts where it plays an important role in protein synthesis dependent synaptic plasticity and senescence respectively. Focusing on the function of CPEB and its role in mRNA polyadenylation during human cellular senescence, the following dissertation documents the important finding that CPEB is required for the normal polyadenylation of p53 mRNA necessary for its normal translation and onset of senescence. Cells that lack CPEB have abnormal levels of mitochondria and ROS production, which are demonstrated to arise from the direct result of hypomorphic p53 levels. Finally, in an attempt to recapitulate the model of CPEB complex polyadenylation in human somatic cells, I unexpectedly find that Gld-2, a poly(A) polymerase required for CPEB-mediated polyadenylation in Xenopus laevis oocytes, is not required for p53 polyadenylation, but instead regulates the stability of a microRNA that in turn regulates CPEB mRNA translation. Furthermore, I demonstrate that CPEB requires Gld-4 for the normal polyadenylation and translation of p53 mRNA.
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Kan, Ming-Chung. "Analysis of CPEB Family Protein Member CPEB4 Function in Mammalian Neurons: A Dissertation." eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/362.
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Local protein synthesis is required for long-term memory formation in the brain. One protein family, Cytoplasmic Polyadenylation Element binding Protein (CPEB) that regulates protein synthesis is found to be important for long-term memory formation possibly through regulating local protein synthesis in neurons. The well-studied member of this family, CPEB1, mediates both translational repression and activation of its target mRNAs by regulating mRNA polyadenylation. Mouse with CPEB1 KO shows defect in memory extinction but not long-term memory formation. Three more CPEB1 homologs (CPEB2-4) are identified in mammalian system. To test if CPEB2-4 may have redundant role in replacing CPEB1 in mediating local protein synthesis, the RNA binding specificity of these homologs are studied by SELEX. The result shows CPEB2-4 bind to RNAs with consensus sequence that is distinct from CPE, the binding site of CPEB1. This distinction RNA binding specificity between CPEB1 and CPEB2-4 suggests CPEB2-4 cannot replace CPEB1 in mediating local protein synthesis. For CPEB2-4 have distinct RNA binding specificity compared to CPEB1, they are referred as CPEB-like proteins. One of CPEB-like protein, CPEB3, binds GluR2 mRNA and represses its translation. The subcellular localization of CPEB family proteins during glutamate over stimulation is also studied. The CPEB family proteins are identified as nucleus/cytoplasm shuttling proteins that depend on CRM1 for nuclear export. CPEB-like proteins share similar nuclear export ciselement that is not present in CPEB1. Over-stimulation of neuron by glutamate induces the nuclear accumulation of CPEB family proteins possibly through disrupted nuclear export. This nuclear accumulation of CPEB family protein is induced by imbalance of calcium metabolism in the neurons. Biochemical and cytological results suggest CPEB4 protein is associated with ER membrane peripherally in RNA independent manner. This research provides general description of biochemical, cytological properties of CPEB family proteins.
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Zheng, Jun. "The Establishment and characterization of a novel plant in vitro cleavage and polyadenylation assay system." Miami University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=miami1281031132.
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Forbes, Kevin Patrick. "Characterization of plant polyadenylation transacting factors--factors that modify poly(A)polymerse activity." Lexington, Ky. : [University of Kentucky Libraries], 2005. http://lib.uky.edu/ETD/ukyplph2005d00278/etd.pdf.
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Thesis (Ph. D.)--University of Kentucky, 2005.Title from document title page (viewed on November 7, 2005). Document formatted into pages; contains vi, 135 p. : ill. Includes abstract and vita. Includes bibliographical references (p. 113-133).
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Zhao, Hongwei. "A Proteomic Study of Plant Messenger RNA Cleavage and Polyadenylation Specificity Factors and the Establishment of an In Vitro Cleavage Assay System." Oxford, Ohio : Miami University, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=miami1218547019.
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Anta, Rodríguez Héctor. "Characterization of the role of the CPEB family of RNA-binding proteins in neurodegeneration." Doctoral thesis, Universitat Pompeu Fabra, 2016. http://hdl.handle.net/10803/664116.
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Alzheimer’s disease (AD) is the most common type of dementia in the elderly. It is associated to a progressive loss of memory, problems in learning and behaviour changes. This disease is characterized by the accumulation of extracellular amyloid β (Aβ) aggregates and intracellular deposits of hyperphosphorylated Tau protein. Both aggregates trigger neuronal apoptosis and glial inflammation, leading to the cognitive decline found in AD patients. Interestingly, the serine protease tissue plasminogen activator (tPA), which is induced by Aβ, has been found to play a dual, dose-dependent role in the disease. Physiological levels of tPA confers neuroprotection through plasmin generation and Aβ degradation. In contrast, high doses of tPA activate intracellular signalling pathways in neurons and glial cells, inducing neuronal apoptosis and inflammation. However, the molecular mechanisms that govern the regulation of tPA expression in AD have still not been fully elucidated. In this work, we demonstrate that Aβ-induced tPA expression is regulated by translational control. In particular, our results show that CPEB1 and CPEB4, two members of the cytoplasmic polyadenylation element binding protein (CPEB) family of RNA-binding proteins, control local tPA synthesis in response to Aβ. Specifically, Aβ promotes tPA mRNA translation in the dendritic spines through synaptic polyadenylation and synaptic cleavage and polyadenylation, a mechanism that is impaired in the absence of CPEB1 or CPEB4. Our results also demonstrate that the pre-mRNA 3'-end processing machinery required for the efficient cleavage and polyadenylation of mRNAs is also present in the synaptic terminals. Finally, we have found that, similarly to tPA, CPEB4 is upregulated in the synaptic terminals in response Aβ and in vivo in the brain of AD patients.La enfermedad de Alzheimer (EA) es la demencia más común en la tercera edad. Está asociada a una pérdida progresiva de memoria, problemas de aprendizaje y cambios de comportamiento. Esta enfermedad se caracteriza por la acumulación de agregados extracelulares de proteína β-amiloide (Aβ) y depósitos intracelulares de proteína Tau hiperfosforilada. Ambos agregados inducen apoptosis neuronal e inflamación mediada por las células de la glia, lo cual desencadena el declive cognitivo característico de los enfermos de EA. En este sentido, se ha demostrado que una serina proteasa, el activador del plasminógeno tisular (del inglés "tissue plasminogen activator", tPA), cuya expresión se induce por Aβ, juega un doble papel clave en la enfermedad en función de sus niveles. Por un lado, unos niveles fisiológicos de tPA pueden ser neuroprotectores a través de la generación de plasmina, con la consiguiente degradación del Aβ. Por otro lado, unos niveles altos de tPA activan cascadas de señalización intracelular en neuronas y células de la glia, lo que induce apoptosis neuronal e inflamación. Los mecanismos moleculares que rigen la regulación de la expresión de tPA en la EA no se conocen con claridad. En este trabajo, demostramos que la expresión de tPA inducida por Aβ está regulada por control traducional. En concreto, nuestros resultados muestran que CPEB1 y CPEB4, dos miembros de la familia CPEB de proteínas de unión a RNA (del inglés "cytoplasmic polyadenylation element binding, CPEB), controlan la síntesis de tPA en respuesta a Aβ. Concretamente, el Aβ promueve la traducción del ARNm de tPA en las espinas sinápticas a través de poliadenilación sináptica, y procesamiento y poliadenilación alternativos sinápticos, un mecanismo que se ve interrumpido en ausencia de CPEB1 o CPEB4. Nuestros resultados también demuestran que la maquinaria de procesamiento de los extremos 3' del pre-ARNm necesaria para llevar a cabo este proceso está presente en los terminales sinápticos. Por último, hemos encontrado que, al igual que tPA, CPEB4 se sobreexpresa en los terminales sinápticos en respuesta a Aβ, así como en el cerebro de pacientes con EA.
Books on the topic "MRNA Cleavage and Polyadenylation Factors"
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service), ScienceDirect (Online, ed. RNA turnover in eukaryotes: Nucleases, pathways and analysis of mRNA decay. San Diego, Calif: Academic, 2008.
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Kiledjian, Megerditch, and Lynne E. Maquat. RNA Turnover in Eukaryotes: Analysis of Specialized and Quality Control RNA Decay Pathways. Elsevier Science & Technology Books, 2011.
Find full textBook chapters on the topic "MRNA Cleavage and Polyadenylation Factors"
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Keller, Walter. "3′-End Cleavage and polyadenylation of nuclear Messenger RNA Precursors." In Pre-mRNA Processing, 113–34. Berlin, Heidelberg: Springer Berlin Heidelberg, 1995. http://dx.doi.org/10.1007/978-3-662-22325-3_7.
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Na, Mihwa, Susana T. Valente, and Kevin Ryan. "Optimizing In Vitro Pre-mRNA 3′ Cleavage Efficiency: Reconstitution from Anion-Exchange Separated HeLa Cleavage Factors and from Adherent HeLa Cell Nuclear Extract." In Methods in Molecular Biology, 179–98. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-6518-2_14.
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Cai, Zhiqiang, Byung Ran So, and Gideon Dreyfuss. "Comprehensive RNP profiling in cells identifies U1 snRNP complexes with cleavage and polyadenylation factors active in telescripting." In Methods in Enzymology, 325–47. Elsevier, 2021. http://dx.doi.org/10.1016/bs.mie.2021.04.017.
Full textConference papers on the topic "MRNA Cleavage and Polyadenylation Factors"
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Ni, Thomas K., and Charlotte Kuperwasser. "Abstract A48: Role of premature mRNA cleavage and alternative polyadenylation in driving breast cancer." In Abstracts: AACR Special Conference: Advances in Breast Cancer; October 17-20, 2015; Bellevue, WA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1557-3125.advbc15-a48.
Full textReports on the topic "MRNA Cleavage and Polyadenylation Factors"
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Schuster, Gadi, and David Stern. Integration of phosphorus and chloroplast mRNA metabolism through regulated ribonucleases. United States Department of Agriculture, August 2008. http://dx.doi.org/10.32747/2008.7695859.bard.
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New potential for engineering chloroplasts to express novel traits has stimulated research into relevant techniques and genetic processes, including plastid transformation and gene regulation. This proposal continued our long time BARD-funded collaboration research into mechanisms that influence chloroplast RNA accumulation, and thus gene expression. Previous work on cpRNA catabolism has elucidated a pathway initiated by endonucleolytic cleavage, followed by polyadenylation and exonucleolytic degradation. A major player in this process is the nucleus-encoded exoribonuclease/polymerasepolynucleotidephoshorylase (PNPase). Biochemical characterization of PNPase has revealed a modular structure that controls its RNA synthesis and degradation activities, which in turn are responsive to the phosphate (P) concentration. However, the in vivo roles and regulation of these opposing activities are poorly understood. The objectives of this project were to define how PNPase is controlled by P and nucleotides, using in vitro assays; To make use of both null and site-directed mutations in the PNPgene to study why PNPase appears to be required for photosynthesis; and to analyze plants defective in P sensing for effects on chloroplast gene expression, to address one aspect of how adaptation is integrated throughout the organism. Our new data show that P deprivation reduces cpRNA decay rates in vivo in a PNPasedependent manner, suggesting that PNPase is part of an organismal P limitation response chain that includes the chloroplast. As an essential component of macromolecules, P availability often limits plant growth, and particularly impacts photosynthesis. Although plants have evolved sophisticated scavenging mechanisms these have yet to be exploited, hence P is the most important fertilizer input for crop plants. cpRNA metabolism was found to be regulated by P concentrations through a global sensing pathway in which PNPase is a central player. In addition several additional discoveries were revealed during the course of this research program. The human mitochondria PNPase was explored and a possible role in maintaining mitochondria homeostasis was outlined. As polyadenylation was found to be a common mechanism that is present in almost all organisms, the few examples of organisms that metabolize RNA with no polyadenylation were analyzed and described. Our experiment shaded new insights into how nutrient stress signals affect yield by influencing photosynthesis and other chloroplast processes, suggesting strategies for improving agriculturally-important plants or plants with novel introduced traits. Our studies illuminated the poorly understood linkage of chloroplast gene expression to environmental influences other than light quality and quantity. Finely, our finding significantly advanced the knowledge about polyadenylation of RNA, the evolution of this process and its function in different organisms including bacteria, archaea, chloroplasts, mitochondria and the eukaryotic cell. These new insights into chloroplast gene regulation will ultimately support plant improvement for agriculture
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Hansen, Peter J., and Zvi Roth. Use of Oocyte and Embryo Survival Factors to Enhance Fertility of Heat-stressed Dairy Cattle. United States Department of Agriculture, August 2011. http://dx.doi.org/10.32747/2011.7697105.bard.
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The overall goal was to identify survival factors that can improve pregnancy success following insemination or embryo transfer in lactating dairy cows exposed to heat stress. First, we demonstrated that oocytes are actually damaged by elevated temperature in the summer. Then we tested two thermoprotective molecules for their effect on oocyte damage caused by heat shock. One molecule, ceramide was not thermoprptective. Another, insulin-like growth factor-1 (IGF) reduced the effects of heat shock on oocyte apoptosis and oocyte cleavage when added during maturation. We also used lactating cows exposed to heat stress to determine whether bovine somatotropin (bST), which increases IGF1 levels in vivo, would improve fertility in summer. Cows treated with bST received a single injection at 3 days before insemination. Controls received no additional treatment. Treatment with bST did not significantly increase the proportion of inseminated cows diagnosed pregnant although it was numerically greater for the bST group (24.2% vs 17.8%, 124–132 cows per group). There was a tendency (p =0.10) for a smaller percent of control cows to have high plasma progesterone concentrations (≥ 1 ng/ml) at Day 7 after insemination than for bST-treated cows (72.6 vs 81.1%). When only cows that were successfully synchronized were considered, the magnitude of the absolute difference in the percentage of inseminated cows that were diagnosed pregnant between bST and control cows was reduced (24.8 vs 22.4% pregnant for bST and control). Results failed to indicate a beneficial effect of bST treatment on fertility of lactating dairy cows. In another experiment, we found a tendency for addition of IGF1 to embryo culture medium to improve embryonic survival after embryo transfer when the experiment was done during heat stress but not when the experiment was done in the absence of heat stress. Another molecule tested, granulocyte-macrophage colony-stimulating factor (GM-CSF; also called colony-stimulating factor-2), improved embryonic survival in the absence of heat stress. We also examined whether heat shock affects the sperm cell. There was no effect of heat shock on sperm apoptosis (programmed cell death) or on sperm fertilizing ability. Therefore, effects of heat shock on sperm function after ejaculation if minimal. However, there were seasonal changes in sperm characteristics that indicates that some of the decrease in dairy cow fertility during the summer in Israel is due to using semen of inferior quality. Semen was collected from five representative bulls throughout the summer (August and September) and winter (December and January). There were seasonal differences in ion concentration in seminal plasma and in the mRNA for various ion channels known to be involved in acrosome reactions. Furthermore, the proportion of sperm cells with damaged acrosomes was higher in post-thaw semen collected in the summer than in its counterpart collected in winter (54.2 ± 3.5% vs. 51.4 ± 1.9%, respectively; P < 0.08Further examination is required to determine whether such alterations are involved in the low summer fertility of dairy cows.
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Meidan, Rina, and Robert Milvae. Regulation of Bovine Corpus Luteum Function. United States Department of Agriculture, March 1995. http://dx.doi.org/10.32747/1995.7604935.bard.
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The main goal of this research plan was to elucidate regulatory mechanisms controlling the development, function of the bovine corpus luteum (CL). The CL contains two different sterodigenic cell types and therefore it was necessary to obtain pure cell population. A system was developed in which granulosa and theca interna cells, isolated from a preovulatory follicle, acquired characteristics typical of large (LL) and small (SL) luteal cells, respectively, as judged by several biochemical and morphological criteria. Experiments were conducted to determine the effects of granulosa cells removal on subsequent CL function, the results obtained support the concept that granulosa cells make a substaintial contribution to the output of progesterone by the cyclic CL but may have a limited role in determining the functional lifespan of the CL. This experimental model was also used to better understand the contribution of follicular granulosa cells to subsequent luteal SCC mRNA expression. The mitochondrial cytochrome side-chain cleavage enzyme (SCC), which converts cholesterol to pregnenolone, is the first and rate-limiting enzyme of the steroidogenic pathway. Experiments were conducted to characterize the gene expression of P450scc in bovine CL. Levels of P450scc mRNA were higher during mid-luteal phase than in either the early or late luteal phases. PGF 2a injection decreased luteal P450scc mRNA in a time-dependent manner; levels were significantly reduced by 2h after treatment. CLs obtained from heifers on day 8 of the estrous cycle which had granulosa cells removed had a 45% reduction in the levels of mRNA for SCC enzymes as well as a 78% reduction in the numbers of LL cells. To characterize SCC expression in each steroidogenic cell type we utilized pure cell populations. Upon luteinization, LL expressed 2-3 fold higher amounts of both SCC enzymes mRNAs than SL. Moreover, eight days after stimulant removal, LL retained their P4 production capacity, expressed P450scc mRNA and contained this protein. In our attempts to establish the in vitro luteinization model, we had to select the prevulatory and pre-gonadotropin surge follicles. The ratio of estradiol:P4 which is often used was unreliable since P4 levels are high in atretic follicles and also in preovulatory post-gonadotropin follicles. We have therefore examined whether oxytocin (OT) levels in follicular fluids could enhance our ability to correctly and easily define follicular status. Based on E2 and OT concentrations in follicular fluids we could more accurately identify follicles that are preovulatory and post gonadotropin surge. Next we studied OT biosynthesis in granulosa cells, cells which were incubated with forskolin contained stores of the precursor indicating that forskolin (which mimics gonadotropin action) is an effective stimulator of OT biosynthesis and release. While studying in vitro luteinization, we noticed that IGF-I induced effects were not identical to those induced by insulin despite the fact that megadoses of insulin were used. This was the first indication that the cells may secrete IGF binding protein(s) which regonize IGFs and not insulin. In a detailed study involving several techniques, we characterized the species of IGF binding proteins secreted by luteal cells. The effects of exogenous polyunsaturated fatty acids and arachidonic acid on the production of P4 and prostanoids by dispersed bovine luteal cells was examined. The addition of eicosapentaenoic acid and arachidonic acid resulted in a dose-dependent reduction in basal and LH-stimulated biosynthesis of P4 and PGI2 and an increase in production of PGF 2a and 5-HETE production. Indomethacin, an inhibitor of arachidonic acid metabolism via the production of 5-HETE was unaffected. Results of these experiments suggest that the inhibitory effect of arachidonic acid on the biosynthesis of luteal P4 is due to either a direct action of arachidonic acid, or its conversion to 5-HETE via the lipoxgenase pathway of metabolism. The detailed and important information gained by the two labs elucidated the mode of action of factors crucially important to the function of the bovine CL. The data indicate that follicular granulosa cells make a major contribution to numbers of large luteal cells, OT and basal P4 production, as well as the content of cytochrome P450 scc. Granulosa-derived large luteal cells have distinct features: when luteinized, the cell no longer possesses LH receptors, its cAMP response is diminished yet P4 synthesis is sustained. This may imply that maintenance of P4 (even in the absence of a Luteotropic signal) during critical periods such as pregnancy recognition, is dependent on the proper luteinization and function of the large luteal cell.