A compendium of conserved cleavage and polyadenylation events in mammalian genes
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ABSTRACT:
PROVIDER: PRJNA435992 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6782970.fastq.gz | Fastqsanger.gz | |||
| SRR6782980.fastq.gz | Fastqsanger.gz | |||
| SRR6782971.fastq.gz | Fastqsanger.gz | |||
| SRR6782981.fastq.gz | Fastqsanger.gz | |||
| SRR6782972.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Cleavage and polyadenylation is essential for 3’ end processing of almost all eukaryotic mRNAs. Recent studies have shown widespread alternative cleavage and polyadenylation (APA) events leading to mRNA isoforms with different 3’UTRs and/or coding sequences. Here we present a compendium of conserved cleavage and polyadenylation sites (PASs) in mammalian genes, based on ~1.2 billion 3’ end sequencing reads from over 360 human, mouse and rat samples. We show that ~80% of mammalian mRNA genes contain at least one conserved PAS, and ~50% have conserved APA events. PAS conservation generally reduces promiscuous 3’ end processing, stabling gene expression levels across species. Conservation of APA correlates with gene age, gene expression features, and gene functions. Genes with certain functions, such as cell morphology, cell proliferation, and mRNA metabolism, are particularly enriched with APA events. While tissue-specific genes typically have a low APA rate, brain-specific genes tend to evolve APA. We show enrichment of mRNA destabilizing motifs in alternative 3’UTR sequences, leading to substantial differences in mRNA stability between 3’UTR APA isoforms. Using conserved PASs, we reveal sequence motifs surrounding APA sites and a preference of adenosine at the cleavage site. Mutations of the U-rich motif around the PAS often accompany APA profile changes between species. Analysis of lncRNA PASs indicates a mechanism of PAS fixation involving evolution of A-rich motifs. Taken together, our results present a comprehensive view of PAS evolution in mammals, and a phylogenic understanding of APA functions.
2018-08-08 | GSE111134 | GEO
Project description:Cleavage and polyadenylation is essential for 3' end processing of almost all eukaryotic mRNAs. Recent studies have shown widespread alternative cleavage and polyadenylation (APA) events leading to mRNA isoforms with different 3' UTRs and/or coding sequences. Here, we present a compendium of conserved cleavage and polyadenylation sites (PASs) in mammalian genes, based on approximately 1.2 billion 3' end sequencing reads from more than 360 human, mouse, and rat samples. We show that ∼80% of mammalian mRNA genes contain at least one conserved PAS, and ∼50% have conserved APA events. PAS conservation generally reduces promiscuous 3' end processing, stabilizing gene expression levels across species. Conservation of APA correlates with gene age, gene expression features, and gene functions. Genes with certain functions, such as cell morphology, cell proliferation, and mRNA metabolism, are particularly enriched with conserved APA events. Whereas tissue-specific genes typically have a low APA rate, brain-specific genes tend to evolve APA. In addition, we show enrichment of mRNA destabilizing motifs in alternative 3' UTR sequences, leading to substantial differences in mRNA stability between 3' UTR isoforms. Using conserved PASs, we reveal sequence motifs surrounding APA sites and a preference of adenosine at the cleavage site. Furthermore, we show that mutations of U-rich motifs around the PAS often accompany APA profile differences between species. Analysis of lncRNA PASs indicates a mechanism of PAS fixation through evolution of A-rich motifs. Taken together, our results present a comprehensive view of PAS evolution in mammals, and a phylogenic perspective on APA functions.
| S-EPMC6169888 | biostudies-literature
Project description:Alternative cleavage and polyadenylation (APA) is a form of transcriptional regulation via shifts in how frequently multiple polyadenylation (polyA) sites within genes are used across biological conditions. APA can result in transcripts with varying length and information content, and has been linked to gene regulation in both cancer and development. To provide a reference for investigating APA in the context of prostate cancer, we performed a genome-wide quantification of polyA site usage using a next generation sequencing technique. By priming the polyA-tails of an RNA library, we mapped cleavage sites and abundances with base-pair resolution across the genomes of one normal prostate and two prostate cancer cell lines. This data can be used to detect APA events among these cell line models, and integration of these data with APA events from clinical prostate cancer samples can lead to candidate genes for future mechanistic studies of the regulation and function of APA in cancer.
2022-12-29 | GSE86180 | GEO
Project description:Alternative cleavage and polyadenylation (APA) results in mRNA isoforms containing different 3’ untranslated regions (3’UTRs) and/or coding sequences. How core cleavage and polyadenylation (C/P) factors regulate APA is not well understood. Using siRNA knockdown coupled with deep sequencing, we found that several C/P factors can play significant roles in 3’UTR-APA. Whereas Pcf11 and Fip1 enhance usage of proximal poly(A) sites (pAs), CFI-25/68, PABPN1, and PABPC1 promote usage of distal pAs. Strong cis element biases were found for pAs regulated by CFI or Fip1, and the distance between pAs plays an important role in APA regulation. In addition, intronic pAs are substantially regulated by splicing factors, with U1 mostly influencing C/P events in 5’ introns and U2 impacting those in efficiently spliced introns. Furthermore, PABPN1 regulates expression of transcripts with pAs near the transcription start site, a property possibly related to its role in RNA degradation. Finally, we found that groups of APA events regulated by C/P factors are also modulated in cell differentiation and development with distinct trends. Together, our results indicate that the abundance of different C/P factors and splicing factors plays diverse roles in APA, and is relevant to APA regulation in biological conditions. knockdown experiments of 23 C/P factors, 3 splicing factors and U1D in mouse C2C12 myoblast cells
2015-04-01 | E-GEOD-62001 | biostudies-arrayexpress
Project description:Cleavage factor II (CF II) is a poorly characterized component of the multi-protein complex catalyzing 3' cleavage and polyadenylation of mammalian mRNA precursors. We have reconstituted CF II as a heterodimer of hPcf11 and hClp1. The heterodimer is active in partially reconstituted cleavage reactions, whereas hClp1 by itself is not. Pcf11 moderately stimulates the RNA 5' kinase activity of hClp1; the kinase activity is dispensable for RNA cleavage. CF II binds RNA with nanomolar affinity. Binding is mediated mostly by the two zinc fingers in the C-terminal region of hPcf11. RNA is bound without pronounced sequence-specificity, but extended G-rich sequences appear to be preferred. We discuss the possibility that CF II contributes to the recognition of cleavage/polyadenylation substrates through interaction with G-rich far-downstream sequence elements.
2020-05-26 | PXD010177 | Pride
Project description:This study is the first to report genome-scale polyadenylation events in S.mediterranea using poly-A position profiling (3P-Seq).Various cis-acting elements such as hexameric PAS & U/GU enrichment after cleavage site were observed to be conserved in planaria.The cleavage site derived from 3P-Seq could be successfully associated with ~38-60% of transcripts (Makers -38%, oxford- 60% and Dresden- 44%).We also investigated the functional consequences of altered 3’UTRs arising from ApA. Around 97 transcripts were observed to undergo coding region alternate polyadenylation (CR-ApA) that resulted in loss of specific domains from proteins (as inferred from pfam domain search). In this study, we also demonstrated that microRNA-mediated regulation might be one of the key factors playing an important role in selection/evolution of alternate 3’UTRs. The 3’ UTR is one of the key regulatory element that decides the fate of mRNA inside a cell. Switching isoforms according to the need of cell and environmental cues could help the cell to adapt. In this study, we also attempted to study the tissue-specific role of ApA pattern in planaria. Due to the limitations associated with isolation of different tissue-specific cells from planaria, we performed a high-throughput microarray analysis across X1, X2 and Xins cell populations. We were clearly able to identify the differential expression pattern of the ApA events across cell population.
2022-10-01 | GSE78261 | GEO
Project description:This study is the first to report genome-scale polyadenylation events in S.mediterranea using poly-A position profiling (3P-Seq).Various cis-acting elements such as hexameric PAS & U/GU enrichment after cleavage site were observed to be conserved in planaria.The cleavage site derived from 3P-Seq could be successfully associated with ~38-60% of transcripts (Makers -38%, oxford- 60% and Dresden- 44%).We also investigated the functional consequences of altered 3’UTRs arising from ApA. Around 97 transcripts were observed to undergo coding region alternate polyadenylation (CR-ApA) that resulted in loss of specific domains from proteins (as inferred from pfam domain search). In this study, we also demonstrated that microRNA-mediated regulation might be one of the key factors playing an important role in selection/evolution of alternate 3’UTRs. The 3’ UTR is one of the key regulatory element that decides the fate of mRNA inside a cell. Switching isoforms according to the need of cell and environmental cues could help the cell to adapt. In this study, we also attempted to study the tissue-specific role of ApA pattern in planaria. Due to the limitations associated with isolation of different tissue-specific cells from planaria, we performed a high-throughput microarray analysis across X1, X2 and Xins cell populations. We were clearly able to identify the differential expression pattern of the ApA events across cell population.
2022-10-01 | GSE78161 | GEO
Project description:The PAF complex (Paf1C) has been shown to regulate chromatin modifications, gene transcription, and PolII elongation. Here, we provide the first genome-wide analysis of chromatin occupancy by the entire PAF complex in mammalian cells. We show that Paf1C is recruited not only to promoters and gene bodies, but also to regions downstream of cleavage/polyadenylation (pA) sites at 3â ends, a profile that sharply contrasted with the yeast complex. Remarkably, our studies identified novel, subunit-specific links between Paf1C and regulation of alternative cleavage and polyadenylation (APA) and upstream antisense transcription. Moreover, we found that depletion of Paf1C subunits also resulted in the accumulation of RNA polymerase II (PolII) over gene bodies, which coincided with APA. Depletion of specific Paf1C subunits leads to global loss of histone H2B ubiquitylation, but surprisingly, there is little impact of Paf1C depletion on other histone modifications, including the tri-methylation of histone H3 on lysines 4 and 36 (H3K4me3 and H3K36me3), previously associated with this complex. Our results provide surprising differences with yeast, while unifying observations that link Paf1C with PolII elongation and RNA processing, and suggest that Paf1C could play a role in protecting transcripts from premature cleavage by preventing PolII accumulation at TSS-proximal pA sites. ChIP-seq, RNA-seq and 3'READS of Paf1C factors in mouse C2C12 myoblast cells
2016-01-15 | E-GEOD-72574 | biostudies-arrayexpress
Project description:Alternative cleavage and polyadenylation (APA) results in mRNA isoforms containing different 3’ untranslated regions (3’UTRs) and/or coding sequences. How core cleavage and polyadenylation (C/P) factors regulate APA is not well understood. Using siRNA knockdown coupled with deep sequencing, we found that several C/P factors can play significant roles in 3’UTR-APA. Whereas Pcf11 and Fip1 enhance usage of proximal poly(A) sites (pAs), CFI-25/68, PABPN1, and PABPC1 promote usage of distal pAs. Strong cis element biases were found for pAs regulated by CFI or Fip1, and the distance between pAs plays an important role in APA regulation. In addition, intronic pAs are substantially regulated by splicing factors, with U1 mostly influencing C/P events in 5’ introns and U2 impacting those in efficiently spliced introns. Furthermore, PABPN1 regulates expression of transcripts with pAs near the transcription start site, a property possibly related to its role in RNA degradation. Finally, we found that groups of APA events regulated by C/P factors are also modulated in cell differentiation and development with distinct trends. Together, our results indicate that the abundance of different C/P factors and splicing factors plays diverse roles in APA, and is relevant to APA regulation in biological conditions.
2015-04-01 | GSE62001 | GEO
Project description:We studied the regulation of pre-messenger RNA 3'-end processing (i.e., cleavage at polyadenylation sites) in response to ultraviolet C irradiation in human cells.
2023-02-06 | GSE203517 | GEO