SAGA DUBm-mediated surveillance regulates prompt export of stress-inducible transcripts for proteostasis

Minhoo Kim,Yoonjung Choi,Daeyoup Lee,Harim Kim

doi:10.1038/s41467-019-10350-6

Minhoo Kim, Yoonjung Choi + Show 2 more

Open Access

https://doi.org/10.1038/s41467-019-10350-6

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Abstract

During stress, prompt export of stress-inducible transcripts is critical for cell survival. Here, we characterize a function of the SAGA (Spt-Ada-Gcn5 acetyltransferase) deubiquitylating module (DUBm) in monitoring messenger ribonucleoprotein (mRNP) biogenesis to regulate non-canonical mRNA export of stress-inducible transcripts. Our genetic and biochemical analyses suggest that there is a functional relationship between Sgf73p of DUBm and the essential mRNA export factor, Yra1p. Under physiological conditions, Sgf73p is critical for the proper chromatin localization and RNA binding of Yra1p, while also quality controlling the biogenesis of mRNPs in conjunction with the nuclear exosome exonuclease, Rrp6p. Under environmental stress, when immediate transport of stress-inducible transcripts is imperative, Sgf73p facilitates the bypass of canonical surveillance and promotes the timely export of necessary transcripts. Overall, our results show that the Sgf73p-mediated plasticity of gene expression is important for the ability of cells to tolerate stress and regulate proteostasis to survive under environmental uncertainty.

Highlights

During stress, prompt export of stress-inducible transcripts is critical for cell survival
In this report, we show that Sgf73p of the SAGA deubiquitylating module directly interacts with the essential mRNA export factor, Yra1p, and is required for its proper chromatin localization and binding of nascent RNA
Upon receipt of an environmental stimulus, such as heat shock stress or galactose induction, Sgf73p initiates the noncanonical mRNA export pathway, which is subject to minimal quality control, and facilitates the prompt export of selective gene sets (Fig. 7)

Summary

Introduction

Prompt export of stress-inducible transcripts is critical for cell survival. Sgf73p is critical for the proper chromatin localization and RNA binding of Yra1p, while quality controlling the biogenesis of mRNPs in conjunction with the nuclear exosome exonuclease, Rrp6p. Upon environmental stress, the canonical mRNA export process is bypassed and immediate export of stress-related transcripts is undertaken to maintain proteostasis and maximize cell survival. During environmental stress, when prompt export of stress-related transcripts is required, Sgf73p promotes a bypass of the canonical mRNA export surveillance and allows immediate export of specific transcripts, including those of molecular chaperone genes. This facilitates cellular proteostasis by acting to unfold protein aggregates in the cytoplasm. Our results collectively show that, in response to a stressful environmental change, Sgf73p orchestrates the selective export of immediate genes by occupying their upstream-activating sequences (UASs), and is crucial to sustaining cell adaptability

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