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Nucleic Acids Res. 2014 Apr;42(8):5043-58. doi: 10.1093/nar/gku124. Epub 2014 Feb 5.

Sumoylation of the THO complex regulates the biogenesis of a subset of mRNPs.

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Institut Jacques Monod, CNRS, UMR 7592, Univ Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France, Ecole Doctorale Gènes Génomes Cellules, Université Paris Sud-11, Orsay, France, Proteomics facility, Institut Jacques Monod, CNRS, UMR 7592, Univ Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France, Department for Systems Biology, Institut de recherches cliniques de Montréal (IRCM), Montreal, Québec, Canada H2W 1R7, Département de Biochimie et Médecine Moléculaire, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada H3T 1J4, Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Québec, Canada H3A 1A3, Université Pierre et Marie Curie, UMR7238, 15, rue de l'Ecole de Médecine, 75006 Paris, France and CNRS, UMR7238, Laboratoire de Génomique des Microorganismes, 75006 Paris, France.


Assembly of messenger ribonucleoparticles (mRNPs) is a pivotal step in gene expression, but only a few molecular mechanisms contributing to its regulation have been described. Here, through a comprehensive proteomic survey of mRNP assembly, we demonstrate that the SUMO pathway specifically controls the association of the THO complex with mRNPs. We further show that the THO complex, a key player in the interplay between gene expression, mRNA export and genetic stability, is sumoylated on its Hpr1 subunit and that this modification regulates its association with mRNPs. Altered recruitment of the THO complex onto mRNPs in sumoylation-defective mutants does not affect bulk mRNA export or genetic stability, but impairs the expression of acidic stress-induced genes and, consistently, compromises viability in acidic stress conditions. Importantly, inactivation of the nuclear exosome suppresses the phenotypes of the hpr1 non-sumoylatable mutant, showing that SUMO-dependent mRNP assembly is critical to allow a specific subset of mRNPs to escape degradation. This article thus provides the first example of a SUMO-dependent mRNP-assembly event allowing a refined tuning of gene expression, in particular under specific stress conditions.

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