PUBLICATION
Alternative polyadenylation alters protein dosage by switching between intronic and 3'UTR sites
- Authors
- de Prisco, N., Ford, C., Elrod, N.D., Lee, W., Tang, L.C., Huang, K.L., Lin, A., Ji, P., Jonnakuti, V.S., Boyle, L., Cabaj, M., Botta, S., Õunap, K., Reinson, K., Wojcik, M.H., Rosenfeld, J.A., Bi, W., Tveten, K., Prescott, T., Gerstner, T., Schroeder, A., Fong, C.T., George-Abraham, J.K., Buchanan, C.A., Hanson-Khan, A., Bernstein, J.A., Nella, A.A., Chung, W.K., Brandt, V., Jovanovic, M., Targoff, K.L., Yalamanchili, H.K., Wagner, E.J., Gennarino, V.A.
- ID
- ZDB-PUB-230218-33
- Date
- 2023
- Source
- Science advances 9: eade4814 (Journal)
- Registered Authors
- Keywords
- none
- Datasets
- GEO:GSE206558, GEO:GSE206559
- MeSH Terms
-
- Exons
- 3' Untranslated Regions
- Animals
- Infant, Newborn
- Introns/genetics
- Humans
- Polyadenylation*
- Zebrafish*/genetics
- Embryo, Nonmammalian
- PubMed
- 36800428 Full text @ Sci Adv
Citation
de Prisco, N., Ford, C., Elrod, N.D., Lee, W., Tang, L.C., Huang, K.L., Lin, A., Ji, P., Jonnakuti, V.S., Boyle, L., Cabaj, M., Botta, S., Õunap, K., Reinson, K., Wojcik, M.H., Rosenfeld, J.A., Bi, W., Tveten, K., Prescott, T., Gerstner, T., Schroeder, A., Fong, C.T., George-Abraham, J.K., Buchanan, C.A., Hanson-Khan, A., Bernstein, J.A., Nella, A.A., Chung, W.K., Brandt, V., Jovanovic, M., Targoff, K.L., Yalamanchili, H.K., Wagner, E.J., Gennarino, V.A. (2023) Alternative polyadenylation alters protein dosage by switching between intronic and 3'UTR sites. Science advances. 9:eade4814.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping