Location of polyadenylation sites within 3’ untranslated regions is linked to biological function in yeast
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PROVIDER: PRJNA1132142 | ENA |
REPOSITORIES: ENA
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Project description:Expression of a typical yeast gene results in ~50 3’ mRNA isoforms that are distinguished by the locations of poly(A) sites within the 3’ untranslated regions (3’ UTRs).The location of poly(A) sites with respect to the translational termination codon varies considerably among genes, but it is unknown whether this has any functional significance.Using hierarchical clustering of 3’ UTRs, we identify eight classes ofS. cerevisiaegenes based on their poly(A) site locations within 3’ UTRs.Genes involved in related biological functions (GO categories) are uniquely over-represented in six of these classes.Similar analysis ofS. pombegenes reveals three classes of 3’ UTRs, all of which show over-representation of functionally related genes.Remarkably,S. cerevisiaeandS. pombehomologs have similar patterns of poly(A) site locations.These observations suggest that the location of poly(A) sites within 3’ UTRs has biological significance.
2024-10-15 | GSE271512 | GEO
Project description:The 3' untranslated regions (3' UTRs) of mRNAs contain cis-acting elements for posttranscriptional regulation of gene expression. Here, we report that mouse genes tend to express mRNAs with longer 3' UTRs as embryonic development progresses. This global regulation is controlled by alternative polyadenylation and coordinates with initiation of organogenesis and aspects of embryonic development, including morphogenesis, differentiation, and proliferation. Using myogenesis of C2C12 myoblast cells as a model, we recapitulated this process in vitro and found that 3' UTR lengthening is likely caused by weakening of mRNA polyadenylation activity. Because alternative 3' UTR sequences are typically longer and have higher AU content than constitutive ones, our results suggest that lengthening of 3' UTR can significantly augment posttranscriptional control of gene expression during embryonic development, such as microRNA-mediated regulation. Two biological replicates of C2C12 growth and differentiation conditions, repesctively
2010-08-31 | E-GEOD-23871 | biostudies-arrayexpress
Project description:The 3' untranslated regions (3' UTRs) of mRNAs contain cis-acting elements for posttranscriptional regulation of gene expression. Here, we report that mouse genes tend to express mRNAs with longer 3' UTRs as embryonic development progresses. This global regulation is controlled by alternative polyadenylation and coordinates with initiation of organogenesis and aspects of embryonic development, including morphogenesis, differentiation, and proliferation. Using myogenesis of C2C12 myoblast cells as a model, we recapitulated this process in vitro and found that 3' UTR lengthening is likely caused by weakening of mRNA polyadenylation activity. Because alternative 3' UTR sequences are typically longer and have higher AU content than constitutive ones, our results suggest that lengthening of 3' UTR can significantly augment posttranscriptional control of gene expression during embryonic development, such as microRNA-mediated regulation.
2010-08-31 | GSE23871 | GEO
Project description:Despite two decades of study, the full scope of RNAi in mammalian cells has remained obscure. Here we combine: 1) Knockout of argonaute (AGO) variants; 2) RNA sequencing analysis of gene expression changes; and 3) Enhanced Crosslinking Immunoprecipitation Sequencing (eCLIP-seq) using anti-AGO2 antibody to identify potential microRNA (miRNA) binding sites. We find that knocking out AGO1, AGO2, and AGO3 are necessary to achieve full impact on gene expression. eCLIP-seq reveals several hundred significant AGO2 associations within 3’-untranslated regions. The standard mechanism of miRNA action would suggest that these associations repress gene expression. Contrary to this expectation, associations between AGO and RNA are poorly correlated with gene repression in wild-type versus knockout cells. Many clusters are associated with increased gene expression in wild-type versus knock out cells, including the strongest cluster within the MYC 3’-UTR. Our results suggest that assumptions about miRNA action should be re-examined.
2020-05-27 | GSE146688 | GEO
Project description:Argonaute Binding within 3’-Untranslated Regions Does Not Predict Gene Repression
| PRJNA611621 | ENA
Project description:The 3' untranslated regions (3' UTRs) of mRNAs play important roles in the regulation of mRNA localization, translation, and stability. Alternative cleavage and polyadenylation (APA) generates mRNAs with different 3' UTRs, but the involvement of this process in stress response has not been clarified. Here, we report that a subset of stress-related genes exhibits 3' UTR extensions of their mRNAs during dehydration stress. These extended 3' UTRs have characteristics of long noncoding RNAs and likely do not interact with miRNAs. Functional studies using T-DNA insertion mutants reveal that they can function as antisense transcripts to repress expression levels of sense genes from the opposite strand, or can activate the transcription of downstream genes from the same strand. Poly(A) signal analysis reveal that mRNAs with 3' UTR extensions have weaker poly(A) signals than mRNAs without 3' UTR extensions. Finally, we show that their biogenesis is partially dependent on a trans-acting factor FPA. Taken together, we report that dehydration stress could induce mRNA 3' UTR extensions, and elucidate a novel function for these stress-induced 3' UTR extensions as long noncoding RNAs in the regulation of their neighboring genes.
2017-04-05 | GSE74864 | GEO
Project description:Peptides encoded by 5’ untranslated regions mediate pain sensitization
| PRJNA480907 | ENA
Project description:Nociceptors are neurons responsible for the detection of pain producing stimuli. Persistent changes in their activity, termed plasticity, benefit survival through injury avoidance and are regulated on a translational basis. Yet, the mRNAs whose translation facilitates plasticity are unknown. Here, we apply ribosome profiling to dorsal root ganglion and identify a small number of transcripts that are selectively translated in response to plasticity mediators. Among them are Arc and Fos, genes implicated in episodic learning in the brain. We demonstrate that the ribosomal S6 kinase 1 is responsible for their production in nociceptors. Blocking S6 driven translation also reduces pain associated behavioral responses in vivo. In addition to translation of coding regions of mRNA, we detect pervasive ribosome occupancy in 5’ untranslated regions. We find that peptides encoded by open reading frames in the 5’ untranslated regions of Calca and Egr2 increase neuronal excitability in vitro and are sufficient to induce pain-like behaviors in vivo. Together, our findings uncover new targets of translational control that drive changes in plasticity and suggest new mechanisms for targeted pain therapeutics that disrupt pain signaling.
2020-02-01 | GSE117043 | GEO
Project description:The 3' untranslated regions (3' UTRs) of mRNAs contain cis-acting elements for posttranscriptional regulation of gene expression. Here, we report that mouse genes tend to express mRNAs with longer 3' UTRs as embryonic development progresses. This global regulation is controlled by alternative polyadenylation and coordinates with initiation of organogenesis and aspects of embryonic development, including morphogenesis, differentiation, and proliferation. Using myogenesis of C2C12 myoblast cells as a model, we recapitulated this process in vitro and found that 3' UTR lengthening is likely caused by weakening of mRNA polyadenylation activity. Because alternative 3' UTR sequences are typically longer and have higher AU content than constitutive ones, our results suggest that lengthening of 3' UTR can significantly augment posttranscriptional control of gene expression during embryonic development, such as microRNA-mediated regulation.
| S-EPMC2669788 | biostudies-literature
Project description:The post-transcriptional fate of messenger RNAs (mRNAs) is largely dictated by their 3' untranslated regions (3'UTRs), which are defined by cleavage and polyadenylation (CPA) of pre-mRNAs. We used poly(A)-position profiling by sequencing (3P-Seq) to map poly(A) sites at eight developmental stages and tissues in the zebrafish. Analysis of over 60 million 3P-Seq reads substantially increased and improved existing 3'UTR annotations, resulting in confidently identified 3'UTRs for more than 78.79% of the annotated protein-coding genes in zebrafish. Most zebrafish genes undergo alternative CPA with more than a thousand genes using different dominant 3'UTRs at different stages. 3'UTRs tend to be shortest in the ovaries and longest in the brain. Isoforms with some of the shortest 3'UTRs are highly expressed in the ovary yet absent in the maternally contributed RNAs of the embryo, perhaps because their 3'UTRs are too short to accommodate a uridine-rich motif required for stability of the maternal mRNA. At two hours post-fertilization, thousands of unique poly(A) sites appear at locations lacking a typical polyadenylation signal, which suggests a wave of widespread cytoplasmic polyadenylation of mRNA degradation intermediates. Our insights into the identities, formation, and evolution of zebrafish 3'UTRs provide a resource for studying gene regulation during vertebrate development. 3P-Seq was used to map the 3' ends of protein-coding genes in the zebrafish genome
2012-06-17 | E-GEOD-37453 | biostudies-arrayexpress