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CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells [PAC-seq]

ABSTRACT: The goal of this study was to compare globlal poly(A) site usage changes upon CPSF1 knockdown in LNCaP, LNCaP95, and 22Rv1 prostate cancer cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE263384 | GEO | 2024/12/20

REPOSITORIES: GEO

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CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells [RNA-seq]

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Prostate cancer cell lines: non-targeting siRNA versus SChLAP1-siRNA treated

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Project description:Here we performed transcriptional profiling of the prostate cancer cell lines LNCaP and 22Rv1 comparing non-targeting siRNA treatment versus siRNAs targeting SWI/SNF complex proteins (SMARCA2, SMARCA4, and SMARCB1). Goal was to determine the effect of SWI/SNF knockdown on gene expression in prostate cancer. Two-condition experiment: non-targeting siRNA versus SWI/SNF-siRNA treated cells. Three SWI/SNF proteins were targeted: SMARCA2, SMARCA4, and SMARB1. Biological replicates: 1 control replicate, 2 treatment replicates per SWI/SNF protein. Technical replicates: 1 replicate per SWI/SNF protein. Cell lines: 22Rv1 and LNCaP.

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Gene expression analysis of prostate cancer cells treated with fatty acid synthase (FASN) inhibitor IPI-9119

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Widespread intronic polyadenylation diversifies immune cell transcriptomes.

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Transcription and polyadenylation in a short human intergenic region.

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Genome-wide mapping of polyadenylation sites in fission yeast reveals widespread alternative polyadenylation.

Project description:Regulatory elements in the 3' untranslated regions (UTRs) of eukaryotic mRNAs influence mRNA localization, translation, and stability. 3'-UTR length 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 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 unique molecular identifiers to ensure that all identified CS originates from individual RNA molecules. I applied this method to create the first comprehensive genome-wide map of polyadenylation sites of the fission yeast Schizosaccharomyces pombe, comprising the analysis of 2,021,000 individual mRNAs that defined 8,883 CSs. CSs were identified for 90% of coding genes and 50% of ncRNAs. Alternative polyadenylation was prevalent in both groups, with 41% and 45% 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 3'-UTR lengths. 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.

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