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Alternative polyadenylation alters protein dosage by switching between intronic and 3' UTR sites

ABSTRACT: Alternative polyadenylation (APA) creates distinct transcripts from the same gene by cleaving the pre-mRNA at poly(A) sites that can lie within the 3' UTR, introns, or exons. Most studies focus on APA within the 3' UTR, but here we show that CPSF6 insufficiency alters protein levels and causes a developmental syndrome by deregulating APA throughout the transcript. In neonatal humans and zebrafish larvae, CPSF6 insufficiency shifts poly(A) site usage between the 3'UTR and internal sites in a pathway-specific manner. Genes associated with neuronal function undergo mostly intronic APA, reducing their expression, while genes associated with heart and skeletal function mostly undergo 3' UTR APA and are upregulated. This suggests that, in healthy conditions, cells toggle between internal and 3'UTR APA to modulate protein expression.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Marko Jovanovic

PROVIDER: MSV000090759 | MassIVE | Mon Nov 21 14:43:00 GMT 2022

REPOSITORIES: MassIVE

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