Published March 29, 2018 | Version v1
Journal article Open

The SAGA/TREX-2 subunit Sus1 binds widely to transcribed genes and affects mRNA turnover globally

  • 1. Gene Expression and RNA Metabolism Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Eduardo Primo Yúfera 3, 46012, Valencia, Spain
  • 2. Departamento de Genética and E.R.I. Biotecmed, Facultad de Biología, Universitat de València, C/Dr. Moliner 50, 46100, Burjassot, Spain
  • 3. Department of Biochemistry and Molecular Biology, Center for Eukaryotic Gene Regulation, The Pennsylvania State University, Pennsylvania, PA, 16802, USA
  • 4. Genomics of Gene Expression Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Eduardo Primo Yúfera 3, 46012, Valencia, Spain
  • 5. Departamento de Bioquímica y Biología Molecular and E.R.I. Biotecmed, Facultad de Biología, Universitat de València, C/Dr. Moliner 50, 46100, Burjassot, Spain
  • 6. Gene Expression and RNA Metabolism Laboratory, Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (CSIC), Jaime Roig 11, 46010, Valencia, Spain

Description

Background: Eukaryotic transcription is regulated through two complexes, the general transcription factor IID (TFIID) and the coactivator Spt–Ada–Gcn5 acetyltransferase (SAGA). Recent findings confirm that both TFIID and SAGA contribute to the synthesis of nearly all transcripts and are recruited genome-wide in yeast. However, how this broad recruitment confers selectivity under specific conditions remains an open question.

Results: Here we find that the SAGA/TREX-2 subunit Sus1 associates with upstream regulatory regions of many yeast genes and that heat shock drastically changes Sus1 binding. While Sus1 binding to TFIID-dominated genes is not affected by temperature, its recruitment to SAGA-dominated genes and RP genes is significantly disturbed under heat shock, with Sus1 relocated to environmental stress-responsive genes in these conditions. Moreover, in contrast to recent results showing that SAGA deubiquitinating enzyme Ubp8 is dispensable for RNA synthesis, genomic run-on experiments demonstrate that Sus1 contributes to synthesis and stability of a wide range of transcripts.

Conclusions: Our study provides support for a model in which SAGA/TREX-2 factor Sus1 acts as a global transcriptional regulator in yeast but has differential activity at yeast genes as a function of their transcription rate or during stress conditions.

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Additional details

Funding

STATEGRA – User-driven Development of Statistical Methods for Experimental Planning, Data Gathering, and Integrative Analysis of Next Generation Sequencing, Proteomics and Metabolomics data 306000
European Commission