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The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE228932 | GEO | 2023/12/21

REPOSITORIES: GEO

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The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking.

Project description:Epithelial-mesenchymal transition (EMT) plays important roles in tumour progression and is orchestrated by dynamic changes in gene expression. While it is well established that post-transcriptional regulation plays a significant role in EMT, the extent of alternative polyadenylation (APA) during EMT has not yet been explored. Using 3' end anchored RNA sequencing, we mapped the alternative polyadenylation (APA) landscape following Transforming Growth Factor (TGF)-β-mediated induction of EMT in human mammary epithelial cells and found APA generally causes 3'UTR lengthening during this cell state transition. Investigation of potential mediators of APA indicated the RNA-binding protein Quaking (QKI), a splicing factor induced during EMT, regulates a subset of events including the length of its own transcript. Analysis of QKI crosslinked immunoprecipitation (CLIP)-sequencing data identified the binding of QKI within 3' untranslated regions (UTRs) was enriched near cleavage and polyadenylation sites. Following QKI knockdown, APA of many transcripts is altered to produce predominantly shorter 3'UTRs associated with reduced gene expression. These findings reveal the changes in APA that occur during EMT and identify a potential role for QKI in this process.

| S-EPMC10732628 | biostudies-literature

The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking [PAT-seq]

Project description:Epithelial-mesenchymal transition (EMT) plays important roles in tumour progression and is orchestrated by dynamic changes in gene expression. While it is well established that post-transcriptional regulation plays a significant role in EMT, the extent of alternative polyadenylation (APA) during EMT has not yet been explored. Using 3’ end anchored RNA sequencing, we mapped the alternative polyadenylation landscape (APA) following TGF-β-mediated induction of EMT in human mammary epithelial cells and found APA generally causes 3’UTR lengthening during this cell state transition. Investigation of potential mediators of APA indicated the RNA-binding protein Quaking (QKI), a splicing factor induced during EMT, regulates a small subset of events including the length of its own transcript. Analysis of QKI CLIP-seq data identified the binding of QKI within 3’UTRs was enriched near cleavage and polyadenylation sites. Following QKI knockdown, APA of many transcripts are altered to produce predominantly shorter 3’UTRs associated with reduced gene expression. These findings reveal the changes in APA that occur during EMT and identify a potential role for QKI in this process.

2023-12-21 | GSE228929 | GEO

The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking [PANQKI_HITS-CLIP]

Project description:Epithelial-mesenchymal transition (EMT) plays important roles in tumour progression and is orchestrated by dynamic changes in gene expression. While it is well established that post-transcriptional regulation plays a significant role in EMT, the extent of alternative polyadenylation (APA) during EMT has not yet been explored. Using 3’ end anchored RNA sequencing, we mapped the alternative polyadenylation landscape (APA) following TGF-β-mediated induction of EMT in human mammary epithelial cells and found APA generally causes 3’UTR lengthening during this cell state transition. Investigation of potential mediators of APA indicated the RNA-binding protein Quaking (QKI), a splicing factor induced during EMT, regulates a small subset of events including the length of its own transcript. Analysis of QKI CLIP-seq data identified the binding of QKI within 3’UTRs was enriched near cleavage and polyadenylation sites. Following QKI knockdown, APA of many transcripts are altered to produce predominantly shorter 3’UTRs associated with reduced gene expression. These findings reveal the changes in APA that occur during EMT and identify a potential role for QKI in this process.

2023-12-21 | GSE228928 | GEO

The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking

Project description:The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking

| PRJNA952202 | ENA

The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking [PANQKI_HITS-CLIP]

Project description:The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking [PANQKI_HITS-CLIP]

| PRJNA952201 | ENA

The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking [PAT-seq]

Project description:The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking [PAT-seq]

| PRJNA952206 | ENA

Dynamic landscape of alternative polyadenylation during retinal development.

Project description:The development of the central nervous system (CNS) is a complex process that must be exquisitely controlled at multiple levels to ensure the production of appropriate types and quantity of neurons. RNA alternative polyadenylation (APA) contributes to transcriptome diversity and gene regulation, and has recently been shown to be widespread in the CNS. However, the previous studies have been primarily focused on the tissue specificity of APA and developmental APA change of whole model organisms; a systematic survey of APA usage is lacking during CNS development. Here, we conducted global analysis of APA during mouse retinal development, and identified stage-specific polyadenylation (pA) sites that are enriched for genes critical for retinal development and visual perception. Moreover, we demonstrated 3'UTR (untranslated region) lengthening and increased usage of intronic pA sites over development that would result in gaining many different RBP (RNA-binding protein) and miRNA target sites. Furthermore, we showed that a considerable number of polyadenylated lncRNAs are co-expressed with protein-coding genes involved in retinal development and functions. Together, our data indicate that APA is highly and dynamically regulated during retinal development and maturation, suggesting that APA may serve as a crucial mechanism of gene regulation underlying the delicate process of CNS development.

| S-EPMC5380485 | biostudies-literature

Posttranscriptional Regulation of HLA-A Protein Expression by Alternative Polyadenylation Signals Involving the RNA-Binding Protein Syncrip.

Project description:Genomic variation in the untranslated region (UTR) has been shown to influence HLA class I expression level and associate with disease outcomes. Sequencing of the 3'UTR of common HLA-A alleles indicated the presence of two polyadenylation signals (PAS). The proximal PAS is conserved, whereas the distal PAS is disrupted within certain alleles by sequence variants. Using 3'RACE, we confirmed expression of two distinct forms of the HLA-A 3'UTR based on use of either the proximal or the distal PAS, which differ in length by 100 bp. Specific HLA-A alleles varied in the usage of the proximal versus distal PAS, with some alleles using only the proximal PAS, and others using both the proximal and distal PAS to differing degrees. We show that the short and the long 3'UTR produced similar mRNA expression levels. However, the long 3'UTR conferred lower luciferase activity as compared with the short form, indicating translation inhibition of the long 3'UTR. RNA affinity pull-down followed by mass spectrometry analysis as well as RNA coimmunoprecipitation indicated differential binding of Syncrip to the long versus short 3'UTR. Depletion of Syncrip by small interfering RNA increased surface expression of an HLA-A allotype that uses primarily the long 3'UTR, whereas an allotype expressing only the short form was unaffected. Furthermore, specific blocking of the proximal 3'UTR reduced surface expression without decreasing mRNA expression. These data demonstrate HLA-A allele-specific variation in PAS usage, which modulates their cell surface expression posttranscriptionally.

| S-EPMC5812486 | biostudies-literature

Transcriptome-wide regulation of pre-mRNA splicing and expression by the RNA-binding protein Quaking during monocyte to macrophage differentiation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-01-04 | E-GEOD-74979 | biostudies-arrayexpress

Regulation of alternative polyadenylation by the C2H2-zinc finger protein Sp1

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-01-28 | GSE165772 | GEO