A stress-dependent postembryonic role for the core CPA factor CFIM-1 in germline integrity

Post-transcriptional processing of pre-mRNAs by alternative polyadenylation (APA) generates a diversity of transcript isoforms at the 3' untranslated region (3'UTR) that can affect their function and stability. The differential enrichment of transcript isoforms has been implicated in diseases ranging from cancer to neurodevelopmental disorders. However, the post-embryonic developmental roles of the core ensemble of cleavage and polyadenylation (CPA) factors that mediate these post-transcriptional changes remain poorly characterized. Here, we report a stress-dependent role for the core CPA factor CFIM-1 in Caenorhabditis elegans germline integrity. Total loss-of-function of cfim-1 elicits a temperature-sensitive sterility phenotype in hermaphrodites but CFIM-1 protein levels do not change with temperature. Sterility is accompanied by sperm, oocyte and germline morphology defects. Surveying the transcriptome of cfim-1(lf) worms revealed changes in transcript isoform abundance for dozens of genes with functions related to the development and maintenance of these structures. Collectively, our findings define a post-embryonic role for a core CPA factor in tissue-specific development.

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Journal
Genetics
Published
2026-01-29
DOI
https://doi.org/10.1093/genetics/iyag022
Primary Topic
RNA Research and Splicing
Type
article
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article

A stress-dependent postembryonic role for the core CPA factor CFIM-1 in germline integrity

Kenneth Y. Kwan, Haruka Nishimura, Anson Sathaseevan, C. Y. Chang et al.
Genetics
RNA Research and Splicing
article

A stress-dependent postembryonic role for the core CPA factor CFIM-1 in germline integrity

Kenneth Y. Kwan, Haruka Nishimura, Anson Sathaseevan, C. Y. Chang, Rhea Ahluwalia, Bin Yu, Alexander Leong, Claudia Makhanko-Tang, W Brent Derry
article en

Abstract

Post-transcriptional processing of pre-mRNAs by alternative polyadenylation (APA) generates a diversity of transcript isoforms at the 3' untranslated region (3'UTR) that can affect their function and stability. The differential enrichment of transcript isoforms has been implicated in diseases ranging from cancer to neurodevelopmental disorders. However, the post-embryonic developmental roles of the core ensemble of cleavage and polyadenylation (CPA) factors that mediate these post-transcriptional changes remain poorly characterized. Here, we report a stress-dependent role for the core CPA factor CFIM-1 in Caenorhabditis elegans germline integrity. Total loss-of-function of cfim-1 elicits a temperature-sensitive sterility phenotype in hermaphrodites but CFIM-1 protein levels do not change with temperature. Sterility is accompanied by sperm, oocyte and germline morphology defects. Surveying the transcriptome of cfim-1(lf) worms revealed changes in transcript isoform abundance for dozens of genes with functions related to the development and maintenance of these structures. Collectively, our findings define a post-embryonic role for a core CPA factor in tissue-specific development.

Genetics
Ontario Institute for Cancer Research (CA), University of British Columbia (CA), University of Toronto (CA), Queen's University (CA), Hospital for Sick Children (CA), BC Children's Hospital (CA)
Openalex Percentile: Top 75%
RNA Research and Splicing
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A stress-dependent postembryonic role for the core CPA factor CFIM-1 in germline integrity — Kenneth Y. Kwan, Haruka Nishimura, et al. · Genetics (2026) | TGRS Research Map | TGRS