SAGA regulates mRNA quality control and export for proteostasis

Abstract

SAGA regulates mRNA Quality Control and Export for Proteostasis Daeyoup Lee Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST) Genome-wide studies indicate that stress-induced genes are SAGA-dominated, and characterized by distinct chromatin structures on promoter regions; however, a detailed molecular mechanism and evolutional advantage of such specialization are in need of further investigation. The deubiquitylating module (DUBm) of SAGA has been implicated to regulate mRNA export, suggesting a more comprehensive role of SAGA in gene expression. Here, we show that Sgf73p of the DUBm physically interacts with the essential mRNA export factor Yra1p and is important for proper recruitment of Yra1p onto chromatin and nascent RNAs. Through its interaction with the nuclear exosome and premature mRNA ribonucleoparticles (mRNPs), Sgf73p is involved in quality control mechanism of mRNP biogenesis. Additionally, we observed significant enrichment of Sgf73 in promoter regions of genes responsible for proteostasis and Sgf73-depleted mutants were more susceptible to heat shock and oxidative stress. Overall, our results provide direct evidence of Sgf73 as an mRNA export surveillance factor and thus the orchestration of gene expression, from transcription activation to elongation and mRNA export, by SAGA.