RRC ID 81850
Author Gallicchio L, Matias NR, Morales-Polanco F, Nava I, Stern S, Zeng Y, Fuller MT.
Title A developmental mechanism to regulate alternative polyadenylation in an adult stem cell lineage.
Journal Genes Dev
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.
Volume 38(13-14)
Pages 655-674
Published 2024-8-20
DOI 10.1101/gad.351649.124
PII gad.351649.124
PMID 39111825
PMC PMC11368245
MeSH Adult Stem Cells / cytology Adult Stem Cells / metabolism Animals Cell Lineage* / genetics Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila melanogaster / cytology Drosophila melanogaster / genetics Drosophila melanogaster / metabolism Gene Expression Regulation, Developmental / genetics Male Polyadenylation* / genetics Spermatocytes* / cytology Spermatocytes* / metabolism Spermatogenesis* / genetics Spermatogonia / cytology Spermatogonia / metabolism mRNA Cleavage and Polyadenylation Factors / genetics mRNA Cleavage and Polyadenylation Factors / metabolism
Resource
Drosophila 10228R-4