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A jack of all trades and a master of some: remodeling of signaling pathways downstream of CFIm 3’ end processing factor

ABSTRACT: The mammalian cleavage factor I (CFIm) has been implicated in alternative polyadenylation (APA) in a broad range of contexts, from cancers to learning deficits and parasite infections. To uncover the molecular pathways that translate CFIm expression levels into these observed phenotypes, we carried out a multi-omics analysis of cell lines in which the CFIm25 (NUDT21) or CFIm68 (CPSF6) subunits were either repressed by siRNA-mediated knockdown or over-expressed from stably integrated constructs. We established that more than 600 genes exhibit CFIm-dependent APA, and they cluster in distinct functional classes related to protein metabolism. The activity of the ERK pathway traces the CFIm concentration, and explains some of the metabolic and proliferation changes induced by CFIm perturbations. Transcripts of miRNA pathway proteins are prominent targets of CFIm-dependent APA. This leads to increased miRNA biogenesis and repressive activity at the same time as 3’ UTRs become shorter upon CFIm depletion. Our study provides a first systematic assessment of the signalling pathways downstream of CFIm to improve our understanding of CFIm-dependent phenotypes.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Alexander Schmidt

LAB HEAD: Alexander Schmidt

PROVIDER: PXD027034 | Pride | 2022-02-11

REPOSITORIES: Pride

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