Combinatorial Analyses of Pre-mRNA Splicing-Defective Mutants Reveal Differential Quantitative Requirements...

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.