title: Perinuclear Mlp proteins downregulate gene expression in response to a defect in mRNA export.
abstract: The mRNA export adaptor Yra1p/REF contributes to nascent mRNP assembly and recruitment of the export receptor Mex67p. yra1 mutants exhibit mRNA export defects and a decrease in LacZ reporter and certain endogenous transcripts. The loss of Mlp1p/Mlp2p, two TPR-like proteins attached to nuclear pores, rescues LacZ mRNA levels and increases their appearance in the cytoplasm, without restoring bulk poly(A)+ RNA export. Chromatin immunoprecipitation, FISH and pulse-chase experiments indicate that Mlps downregulate LacZ mRNA synthesis in a yra1 mutant strain. Microarray analyses reveal that Mlp2p also reduces a subset of cellular transcripts in the yra1 mutant. Finally, we show that Yra1p genetically interacts with the shuttling mRNA-binding protein Nab2p and that loss of Mlps rescues the growth defect of yra1 and nab2 but not other mRNA export mutants. We propose that Nab2p and Yra1p are required for proper mRNP docking to the Mlp platform. Defects in Yra1p prevent mRNPs from crossing the Mlp gate and this block negatively feeds back on the transcription of a subset of genes, suggesting that Mlps link mRNA transcription and export.
authors.affiliation: Department of Cell Biology, Sciences III, University of Geneva, Geneva, Switzerland.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vinciguerra
authors.forename: Nahid
authors.initials: N
authors.lastname: Iglesias
authors.forename: Jurgi
authors.initials: J
authors.lastname: Camblong
authors.forename: Daniel
authors.initials: D
authors.lastname: Zenklusen
authors.forename: Françoise
authors.initials: F
authors.lastname: Stutz
mesh_terms: D015536:Down-Regulation / Q000235:genetics; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D017403:In Situ Hybridization; D007763:Lac Operon / Q000235:genetics; D009154:Mutation / Q000235:genetics; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D020871:RNA Stability; D034443:RNA Transport; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013696:Temperature; D014158:Transcription, Genetic / Q000235:genetics; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: C080988:MLP1 protein, S cerevisiae; C119200:MLP2 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; C105887:YRA1 protein, S cerevisiae; D001616:beta-Galactosidase