Autoregulation of SUS1: a splicing dependent regulation of histone H2B ubiquitination

Abstract

Pre‐messenger RNA splicing is an underappreciated mechanism for regulating gene expression in yeast (Saccharomyces cerevisiae), likely due to the paucity of intron containing genes in this single‐celled eukaryote. However, a growing number of studies suggest that introns play an important role in modulating gene expression under stress conditions. Recently, we have shown that environmental stress modulates splicing of the SUS1, a two‐intron gene in yeast. Sus1p, which is a part of deubiquitination module within the SAGA complex, plays an important role in maintaining proper cellular levels of ubiquitinated H2B. The first intron of SUS1 contains non‐canonical 5’SS and branch point sequences, which leads to retention of the first intron and subsequently limits the production of SUS1 mRNA. Here, we show that increased accumulation of the first intron containing transcript leads to a decrease in SUS1 mRNA production. Interestingly, the first intron containing transcript can be translated to produce truncated Sus1 protein which appears to play a role in SUS1 autoregulation. This study hints at an autoregulatory mechanism of control of SUS1 splicing and demonstrates an important role for regulated splicing in yeast to control histone modification.National Science Foundation awards (NSF CAREER MCB‐0448010 and MCB‐1051921); National Institutes of Health (GM085474)