Authors
Souvik Ghosh, Meric Ataman, Maciej Bak, Anastasiya Börsch, Alexander Schmidt, Katarzyna Buczak, Georges Martin, Beatrice Dimitriades, Christina J Herrmann, Alexander Kanitz, Mihaela Zavolan
Publication date
2022/4/8
Journal
Nucleic acids research
Volume
50
Issue
6
Pages
3096-3114
Publisher
Oxford University Press
Description
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 determine how the CFIm expression levels are translated into these diverse 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 >800 genes undergo coherent APA in response to changes in CFIm levels, 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 fluctuations in cell growth and metabolism that are observed upon CFIm perturbations. Furthermore, multiple transcripts encoding proteins from the miRNA …
Total citations
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