Reference - PMID:41201383 - Combinatorial Analyses of Pre-mRNA Splicing-Defective Mutants Reveal Differential Quantitative Requirements for Shelterin in Distinct Telomere Functions.
Reference summary
- PubMed ID
- PMID:41201383
- Title
- Combinatorial Analyses of Pre-mRNA Splicing-Defective Mutants Reveal Differential Quantitative Requirements for Shelterin in Distinct Telomere Functions.
- Authors
- Takeuchi M, Otsubo Y, Kanoh J
- Citation
- Genes Cells 2025 Nov;30(6):e70064
- Publication year
- 2025
- Abstract
- Telomeres perform multiple functions to maintain genome stability, including telomere length regulation, chromosome end protection, and meiotic chromosome dynamics. These functions are governed by shelterin, a telomere-binding protein complex. Here, we show that Tls1 and Cay1 act at distinct steps in pre-mRNA splicing, specifically ensuring sufficient protein levels of Schizosaccharomyces pombe shelterin components Rap1 and Poz1, which are critical for telomere maintenance. Accordingly, deletion of tls1 + and cay1 + synergistically reduced Rap1 and Poz1 protein levels. Analyses of the phenotypes of single and double tls1∆ and cay1∆ mutants indicated that different telomere functions vary in their dependence on Rap1 levels: telomere length regulation and, to a lesser extent, meiosis require higher protein abundance, whereas chromosome end protection can be sustained with minimal amounts. These findings reveal a hierarchical requirement for Rap1 across telomere functions.
