High-Throughput Sequencing of microRNAs and Alternative Cleavage and Polyadenylation Reveal the Mechanism of Post-Transcription Regulations in Colorectal Cancer Patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE130084 | GEO | 2019/04/25
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the following subset Series: GSE27452: Genome-wide maps of polyadenylation sites in control and PABPN1kd cells GSE32302: Genome-wide maps of polyadenylation sites in OPMD-model and control mice Refer to individual Series
2012-04-14 | E-GEOD-32303 | biostudies-arrayexpress
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
Project description:Genes containing multiple polyadenylation (polyA) sites express mRNA isoforms with variable 3’ untranslated regions (3’UTRs). We found that short and long 3’UTR isoforms were relatively more abundant when genes were highly and lowly expressed, respectively, in human and mouse cells. Consistently, upregulated and downregulated genes were more likely to have shortened and lengthened 3’UTRs, respectively, when genes changed expression under different cell conditions or in response to extracellular stimuli. Using nuclear run-on assays, we found that RNA polymerase II (Pol II) was more likely to pause at the polyA site of highly expressed genes than that of lowly expressed ones. Moreover, in line with the difference in polyA site usage, highly expressed genes tend to have higher H3K4me3 and H3K36me3 levels but a lower density of nucleosome around promoter-proximal polyA sites relative to distal ones. Taken together, our results indicate that the efficiency of 3’ end processing is generally coupled to transcriptional activity, leading to modulation of polyA site choice by transcription and thus connecting transcriptional control with post-transcriptional regulation via pre-mRNA processing. Nascent RNA sequencing of C2C12 cell
2011-08-15 | E-GEOD-26512 | biostudies-arrayexpress
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. 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:Alternative cleavage and polyadenylation (APA) is emerging as an important mechanism of gene regulation in eukaryotes and plays important regulatory roles in human development and diseases. Despite the widespread application of Second Generation Sequencing (SGS) technology for polyadenylation site identification, matching each identified polyadenylation site within a gene to its derived isoform remains a major challenge. To achieve the isoform-resolved APA analysis, we developed a tool termed “IDP-APA” that constructs truly expressed isoforms and identifies polyadenylation sites by integrating the respective strengths of Third Generation Sequencing (TGS) long reads and SGS short reads. Compared to existing tools, IDP-APA demonstrated superior performance in both isoform reconstruction and polyadenylation site identification. Applications to human embryonic stem cells, breast cancer cells and brain tissue from a patient with Alzheimer’s disease revealed prevalent APA events and cell-/tissue-specific APA patterns, especially in an isoform-resolved way.
2017-06-01 | GSE97688 | GEO
Project description:Purpose: Quiescence is a state of reversible cell cycle exit. Levels of polyadenylation factors decreases when proliferating cells become quiescent. The goals of this study are to determine the differential use of polyadenylation sites (changes in alternative polyadenylation) in quiescent vs. proliferating cells and also upon knockdown of polyadenylation factors. Methods: Two biological replicates of human dermal fibroblasts (12-1 and 12-3) were used for polyadeylation-site enriched RNA-seq on an Illumina HiSeq 2500 to compare quiescent vs. proliferating cells and polyadenylation factor knockdown vs. control cells. The reads were aligned to the human genome (hg19) uisng Tophat (2.0.14). The resulting bam files were used as an input to a python script provided by Gruber et al. (PMID: 27382025) to determine the counts for each polyadenylation site. Results: We observed a shift toward greater use of distal polyadenylation sites when the fibroblasts entered quiescence. We observed significant overlap between the genes that shift to greater distal site use with quiescence and CstF-64 or CPSF73 knockdown. Conclusions: The shift to greater distal site use with quiescence may reflect in part the reduced levels of cleavage and polyadenylation factors.
2018-08-28 | GSE117033 | GEO
Project description:Genes containing multiple polyadenylation (polyA) sites express mRNA isoforms with variable 3’ untranslated regions (3’UTRs). We found that short and long 3’UTR isoforms were relatively more abundant when genes were highly and lowly expressed, respectively, in human and mouse cells. Consistently, upregulated and downregulated genes were more likely to have shortened and lengthened 3’UTRs, respectively, when genes changed expression under different cell conditions or in response to extracellular stimuli. Using nuclear run-on assays, we found that RNA polymerase II (Pol II) was more likely to pause at the polyA site of highly expressed genes than that of lowly expressed ones. Moreover, in line with the difference in polyA site usage, highly expressed genes tend to have higher H3K4me3 and H3K36me3 levels but a lower density of nucleosome around promoter-proximal polyA sites relative to distal ones. Taken together, our results indicate that the efficiency of 3’ end processing is generally coupled to transcriptional activity, leading to modulation of polyA site choice by transcription and thus connecting transcriptional control with post-transcriptional regulation via pre-mRNA processing.
2011-08-15 | GSE26512 | GEO
Project description:Most mammalian genes display alternative cleavage and polyadenylation (APA). Previous studies have indicated preferential expression of APA isoforms with short 3âUTRs in testes. Here we show widespread shortening of 3âUTR by APA during the first wave of spermatogenesis in mouse, with 3âUTRs being the shortest in spermatids. Shortening of 3âUTR eliminates destabilizing elements, such as U-rich elements and transposable elements, which appear to be highly potent for transcript elimination during spermatogenesis. We additionally found widespread regulation of APA in introns and global activation of upstream antisense transcripts during spermatogenesis. Interestingly, genes that display 3âUTR shortening tend to have higher levels of H3K4me3, consistent with the open chromatin feature previously observed in spermatids. Since genes with 3âUTR shortening tend to have functions important for further sperm development after spermatids, when transcription is halted, this result indicates that expression of short, stable mRNAs may serve the purpose of mRNA storage for later translation. Thus, APA in spermatogenesis connects regulation of chromatin status with post-transcriptional control, and impacts sperm maturation. 3'READS of 1 week to 6 week of testis development
2016-01-11 | E-GEOD-73973 | biostudies-arrayexpress
Project description:To understand how U4 snRNP regulates premature cleavage and polyadenylation of pre-mRNAs at the transcriptome wide, we conducted RNAPII ChIP-seq analysis on control, U1 and U4-AMO treated samples.
2024-06-26 | GSE262384 | GEO