title: Nuclear pore components affect distinct stages of intron-containing gene expression.
abstract: Several nuclear pore-associated factors, including the SUMO-protease Ulp1, have been proposed to prevent the export of intron-containing messenger ribonucleoparticles (mRNPs) in yeast. However, the molecular mechanisms of this nuclear pore-dependent mRNA quality control, including the sumoylated targets of Ulp1, have remained unidentified. Here, we demonstrate that the apparent 'pre-mRNA leakage' phenotype arising upon ULP1 inactivation is shared by sumoylation mutants of the THO complex, an early mRNP biogenesis factor. Importantly, we establish that alteration of THO complex activity differentially impairs the expression of intronless and intron-containing reporter genes, rather than triggering bona fide 'pre-mRNA leakage'. Indeed, we show that the presence of introns within THO target genes attenuates the effect of THO inactivation on their transcription. Epistasis analyses further clarify that different nuclear pore components influence intron-containing gene expression at distinct stages. Ulp1, whose maintenance at nuclear pores depends on the Nup84 complex, impacts on THO-dependent gene expression, whereas the nuclear basket-associated Mlp1/Pml39 proteins prevent pre-mRNA export at a later stage, contributing to mRNA quality control. Our study thus highlights the multiplicity of mechanisms by which nuclear pores contribute to gene expression, and further provides the first evidence that intronic sequences can alleviate early mRNP biogenesis defects.
authors.affiliation: Institut Jacques Monod, CNRS, UMR 7592, Univ Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Bonnet
authors.affiliation: 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, 91400 Orsay, France.
authors.forename: Hugo
authors.initials: H
authors.lastname: Bretes
authors.affiliation: Institut Jacques Monod, CNRS, UMR 7592, Univ Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France palancade.benoit@ijm.univ-paris-diderot.fr.
authors.forename: Benoit
authors.initials: B
authors.lastname: Palancade
mesh_terms: D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D007438:Introns; D009154:Mutation; D022022:Nuclear Pore / Q000201:enzymology; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D058207:Sumoylation; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C063494:HPR1 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; C026452:messenger ribonucleoprotein; C068359:MFT1 protein, S cerevisiae; D003546:Cysteine Endopeptidases; C118083:Ulp1 protease
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