1. A developmental mechanism to regulate alternative polyadenylation in an adult stem cell lineage.
- Author
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Gallicchio L, Matias NR, Morales-Polanco F, Nava I, Stern S, Zeng Y, and Fuller MT
- 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
- 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., (© 2024 Gallicchio et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2024
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