Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA130597 | ENA |
REPOSITORIES: ENA
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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:3’ untranslated regions (3’UTRs) are critical elements of most messenger RNA species and can contain binding sites for RNA-binding proteins (RBP) and microRNAs that affect various aspects of RNA life cycles including transcript stability. Cells of the adaptive immune system undergo massive expansion during the effector phase of the immune response and dynamically modify their 3’UTRs in a response to T cell receptor activation. Whether this phenomenon is a secondary effect of proliferation or a mechanism to directly regulate the abundance of specific mRNAs remains unclear. To study 3’UTR dynamics in T helper cells we investigated division-dependent alternative polyadenylation and observed a transient character of global 3’UTR shortening/lengthening in T helper cells that return to a naïve-like polyadenylation state after effector phase expansion. We also showed that 3’UTR lengthening is associated with higher transcript abundance and post-transcriptional regulation than 3’UTR shortening. Sequence analysis of conserved microRNA and RBP binding sites located within varying 3’ UTR regions highlighted the putative involvement of several microRNAs during this process. Our study emphasizes the value of polyadenylation isoforms analysis for understanding cell behaviors, revealing new aspects of the highly complex interplay of transcriptional and post-transcriptional layers in triggering transcript abundance.
2023-11-06 | GSE183424 | GEO
Project description:The tumorigenesis of small intestinal neuroendocrine tumors (NETs) is poorly understood. Recent studies have associated alternative polyadenylation with proliferation, cell transformation and cancer. Polyadenylation is the process in which the pre-mRNA is cleaved at a polyA site and a polyA tail is added. Genes with two or more polyA sites can undergo alternative polyadenylation. This produces two or more distinct mRNA isoforms with different 3M-bM-^@M-^Y untranslated regions. Additionally, alternative polyadenylation can also produce mRNAs containing different 3M-bM-^@M-^Y-terminal coding regions. Therefore, alternative polyadenylation alters both the repertoire and the expression level of proteins. Here we used high-throughput sequencing data to map polyA sites and characterize polyadenylation genome-wide in three small intestinal neuroendocrine tumors and a reference sample. In the tumors sixteen genes showed significant changes of alternative polyadenylation pattern, which lead to either the 3M-bM-^@M-^Y truncation of mRNA coding regions or 3M-bM-^@M-^Y untranslated regions. Among these, 11 genes had been previously associated with cancer, with 4 genes being known tumor suppressors: DCC, PDZD2, MAGI1 and DACT2. We validated the alternative polyadenylation in 3 out of 3 cases with Q-RT-PCR. Our findings suggest that changes of alternative polyadenylation pattern in these 16 genes could be involved in the tumorigenesis of small intestinal neuroendocrine tumors. Furthermore, they also point to alternative polyadenylation as a new target for both diagnostic and treatment of small intestinal neuroendocrine tumors. The identified genes with alternative polyadenylation specific to the small intestinal neuroendocrine tumors could be further tested as diagnostic markers and drug targets for disease prevention and treatment. PolyA-seq profiling of 3 human neuroendocrine tumors compared and pituitary using Direct RNA Sequencing from Helicos Biosciences Technology
2014-04-10 | E-GEOD-56657 | biostudies-arrayexpress
Project description:The tumorigenesis of small intestinal neuroendocrine tumors (NETs) is poorly understood. Recent studies have associated alternative polyadenylation with proliferation, cell transformation and cancer. Polyadenylation is the process in which the pre-mRNA is cleaved at a polyA site and a polyA tail is added. Genes with two or more polyA sites can undergo alternative polyadenylation. This produces two or more distinct mRNA isoforms with different 3’ untranslated regions. Additionally, alternative polyadenylation can also produce mRNAs containing different 3’-terminal coding regions. Therefore, alternative polyadenylation alters both the repertoire and the expression level of proteins. Here we used high-throughput sequencing data to map polyA sites and characterize polyadenylation genome-wide in three small intestinal neuroendocrine tumors and a reference sample. In the tumors sixteen genes showed significant changes of alternative polyadenylation pattern, which lead to either the 3’ truncation of mRNA coding regions or 3’ untranslated regions. Among these, 11 genes had been previously associated with cancer, with 4 genes being known tumor suppressors: DCC, PDZD2, MAGI1 and DACT2. We validated the alternative polyadenylation in 3 out of 3 cases with Q-RT-PCR. Our findings suggest that changes of alternative polyadenylation pattern in these 16 genes could be involved in the tumorigenesis of small intestinal neuroendocrine tumors. Furthermore, they also point to alternative polyadenylation as a new target for both diagnostic and treatment of small intestinal neuroendocrine tumors. The identified genes with alternative polyadenylation specific to the small intestinal neuroendocrine tumors could be further tested as diagnostic markers and drug targets for disease prevention and treatment.
2014-04-10 | GSE56657 | GEO
Project description:Regulatory elements in the 3M-^R untranslated regions (UTRs) of eukaryotic mRNAs influence mRNA localization, translation, and stability. The length of these regions is determined by the location at which mRNAs are cleaved and polyadenylated. The use of alternative polyadenylation sites is common, and can be regulated in different situations. I present here a new method to identify cleavage and polyadenylation sites (CSs) at the genome-wide level. The approach is strand-specific, avoids RNA enzymatic modification steps that can introduce sequence-specific biases, and uses molecular barcodes to ensure that every identified CS originates from an individual RNA molecule. I applied to create the first comprehensive genome-wide map of polyadenylation sites in the fission yeast Schizosaccharomyces pombe, comprising the analysis of over two million individual mRNAs that defined 10,422 major CSs. CSs were identified for 90% of coding genes and 15% of non-coding RNAs. Alternative polyadenylation was prevalent in both groups, with 61% and 49% of all detected genes, respectively, displaying more than one CS. The specificity of the cleavage reaction was gene-specific, resulting in highly variable levels of heterogeneity in the length of the 3' UTRs. Finally, I show that for both coding and non-coding genes the most common regulatory motif associated with CSs in fission yeast is the canonical human AAUAAA sequence.
2013-11-19 | E-MTAB-1642 | biostudies-arrayexpress
Project description:In this study, we report that HCMV infection results in widespread alternative splicing (AS), shorter 3′-untranslated regions (3′UTRs) and polyA tail lengthening in host genes and CPEB1 depletion reverses infection-related post-transcriptional changes.
2016-09-17 | GSE86791 | GEO
Project description:Alternative polyadenylation is a widespread mechanism involving about half of the expressed genes, resulting in varying lengths of the 3' UTR and changes of the post-transcriptional processing, localization, miRNA targeting and stability of mRNAs. During neuronal differentiation a variety of mRNAs change the length of their 3' UTR, promoting the longer version of the transcripts. Little is known about polyA+ site usage during differentiation of mammalian neural progenitors. Here we exploit a model of adherent neural stem (ANS) cells, which homogeneously and efficiently differentiate into GABAergic neurons. RNAseq data shows a global trend towards lengthening of the 3’ UTRs during differentiation. Enriched expression of the long 3’ UTR variants of Pes1 and Gng2 was detected in areas of cortical and subcortical neuronal differentiation, respectively, in the mouse brain by two-probes FISH analyses. In Drosophila the choice of polyA+ site has been shown to be regulated by the RNA-binding protein Elav, which inhibits polyadenylation at proximal sites while interacting with paused Pol-II promoters. Among the coding genes upregulated during differentiation of ANS cells we found Elavl3, a neural-specific RNA-binding protein homologous to Drosophila Elav. The silencing of Elavl3 in ANS cells resulted in impaired elongation of the 3’UTR length and delayed neuronal differentiation. These results indicate that choice of the polyA+ site and lengthening of 3’ UTRs is a possible additional mechanism of posttranscriptional RNA modification involved in neuronal differentiation.
2019-01-10 | GSE119073 | GEO
Project description:Alternative polyadenylation has been explored in multiple native and disease transitions. The prevailing hypothesis being that differentiated cells use longer 3’UTRs with more scope for regulation, whereas undifferentiated cells use shorter, less regulated 3’UTRs. Here we describe gene-expression and alternative polyadenylation of human primary myocytes over a time course differentiation. Contrary to expectation, only minor changes to 3’-end choice were detected. To reconcile this finding with published differentiation data in the immortalized C2C12 myocyte cell line, a systematic comparison was undertaken. Less than half the genes differentially expressed in the immortalized model were recapitulated in primary cells, and of these, important metabolic states were either absent, underrepresented or regulated in the opposite direction. A new bioinformatic approach, developed to quantitate the degree of alternative polyadenylation between unrelated experiments demonstrated that alternative polyadenylation was reduced by ~50% with less than 1/10 of the genes that underwent alternative polyadenylation in C2C12 differentiation showing alternative processing in primary muscle differentiation. A possible explanation for this difference was a less pronounced down regulation of the cleavage and polyadenylation factors in the differentiation primary cell. In sum, the data promote the use of primary human myocytes to model muscle biogenesis over immortalized models that may not fully recapitulate human muscle development.
2024-03-12 | GSE168897 | GEO
Project description:Through alternative polyadenylation, human mRNAs acquire longer or shorter 3' untranslated regions, the latter typically associated with higher transcript stability and increased protein production. To understand the dynamics of polyadenylation site usage, we mapped transcriptome?wide both binding sites of 3' end processing factors CPSF?160, CPSF?100, CPSF?73, CPSF?30, Fip1, CstF?64, CstF-64tau, CF Im25, CF Im59, and CF Im68 and 3' end processing sites in HEK293 cells. We found that although binding sites of these factors generally cluster around the poly(A) sites most frequently used in cleavage, CstF?64/CstF-64tau and CF Im proteins have much higher positional specificity compared to CPSF components. Knockdown of CF Im68 induced a systematic use of proximal polyadenylation sites, indicating that changes in relative abundance of a single 3' end processing factor can modulate the length of 3' untranslated regions transcriptome-wide, and suggesting a mechanism behind the previously observed increase in tumor cell invasiveness upon CF Im68 knockdown. 3' ends of transcripts were profiled by high-throughput sequencing in HEK 293 cells under normal conditions, and in HEK 293 cells depleted of 3' end processing factors CF Im 68 and CstF-64.
2012-05-15 | E-GEOD-37037 | biostudies-arrayexpress