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A developmental mechanism to regulate alternative polyadenylation in an adult stem cell lineage.
- Source :
-
Genes & development [Genes Dev] 2024 Aug 20; Vol. 38 (13-14), pp. 655-674. Date of Electronic Publication: 2024 Aug 20. - Publication Year :
- 2024
-
Abstract
- Alternative cleavage and polyadenylation (APA) often results in production of mRNA isoforms with either longer or shorter 3' UTRs from the same genetic locus, potentially impacting mRNA translation, localization, and stability. Developmentally regulated APA can thus make major contributions to cell type-specific gene expression programs as cells differentiate. During Drosophila spermatogenesis, ∼500 genes undergo APA when proliferating spermatogonia differentiate into spermatocytes, producing transcripts with shortened 3' UTRs, leading to profound stage-specific changes in the proteins expressed. The molecular mechanisms that specify usage of upstream polyadenylation sites in spermatocytes are thus key to understanding the changes in cell state. Here, we show that upregulation of PCF11 and Cbc, the two components of cleavage factor II (CFII), orchestrates APA during Drosophila spermatogenesis. Knockdown of PCF11 or cbc in spermatocytes caused dysregulation of APA, with many transcripts normally cleaved at a proximal site in spermatocytes now cleaved at their distal site, as in spermatogonia. Forced overexpression of CFII components in spermatogonia switched cleavage of some transcripts to the proximal site normally used in spermatocytes. Our findings reveal a developmental mechanism where changes in expression of specific cleavage factors can direct cell type-specific APA at selected genes.<br /> (© 2024 Gallicchio et al.; Published by Cold Spring Harbor Laboratory Press.)
- Subjects :
- Animals
Male
Gene Expression Regulation, Developmental genetics
Adult Stem Cells metabolism
Adult Stem Cells cytology
Drosophila Proteins metabolism
Drosophila Proteins genetics
Drosophila melanogaster genetics
Drosophila melanogaster cytology
Drosophila melanogaster metabolism
Spermatogonia cytology
Spermatogonia metabolism
mRNA Cleavage and Polyadenylation Factors metabolism
mRNA Cleavage and Polyadenylation Factors genetics
Polyadenylation genetics
Spermatogenesis genetics
Spermatocytes metabolism
Spermatocytes cytology
Cell Lineage genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1549-5477
- Volume :
- 38
- Issue :
- 13-14
- Database :
- MEDLINE
- Journal :
- Genes & development
- Publication Type :
- Academic Journal
- Accession number :
- 39111825
- Full Text :
- https://doi.org/10.1101/gad.351649.124