Alternative polyadenylation alters protein dosage by switching between intronic and 3'UTR sites.
Sci Adv
; 9(7): eade4814, 2023 02 17.
Article
en En
| MEDLINE
| ID: mdl-36800428
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' untranslated region (3'UTR), introns, or exons. Most studies focus on APA within the 3'UTR; however, 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 up-regulated. This suggests that, under healthy conditions, cells toggle between internal and 3'UTR APA to modulate protein expression.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Pez Cebra
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Poliadenilación
Límite:
Animals
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Humans
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Newborn
Idioma:
En
Año:
2023
Tipo del documento:
Article