title: The exosome associates cotranscriptionally with the nascent pre-mRNP through interactions with heterogeneous nuclear ribonucleoproteins.
abstract: Eukaryotic cells have evolved quality control mechanisms to degrade aberrant mRNA molecules and prevent the synthesis of defective proteins that could be deleterious for the cell. The exosome, a protein complex with ribonuclease activity, is a key player in quality control. An early quality checkpoint takes place cotranscriptionally but little is known about the molecular mechanisms by which the exosome is recruited to the transcribed genes. Here we study the core exosome subunit Rrp4 in two insect model systems, Chironomus and Drosophila. We show that a significant fraction of Rrp4 is associated with the nascent pre-mRNPs and that a specific mRNA-binding protein, Hrp59/hnRNP M, interacts in vivo with multiple exosome subunits. Depletion of Hrp59 by RNA interference reduces the levels of Rrp4 at transcription sites, which suggests that Hrp59 is needed for the exosome to stably interact with nascent pre-mRNPs. Our results lead to a revised mechanistic model for cotranscriptional quality control in which the exosome is constantly recruited to newly synthesized RNAs through direct interactions with specific hnRNP proteins.
authors.affiliation: Department of Molecular Biology and Functional Genomics, Stockholm University, SE-10691 Stockholm, Sweden.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Hessle
authors.forename: Petra
authors.initials: P
authors.lastname: Björk
authors.forename: Marcus
authors.initials: M
authors.lastname: Sokolowski
authors.forename: Ernesto
authors.initials: E
authors.lastname: González de Valdivia
authors.forename: Rebecca
authors.initials: R
authors.lastname: Silverstein
authors.forename: Konstantin
authors.initials: K
authors.lastname: Artemenko
authors.forename: Anu
authors.initials: A
authors.lastname: Tyagi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Maddalo
authors.forename: Leopold
authors.initials: L
authors.lastname: Ilag
authors.forename: Roger
authors.initials: R
authors.lastname: Helbig
authors.forename: Roman A
authors.initials: RA
authors.lastname: Zubarev
authors.forename: Neus
authors.initials: N
authors.lastname: Visa
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D002683:Chironomidae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D011485:Protein Binding; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D029721:Drosophila Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D011498:Protein Precursors; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C547079:Rrp4 protein, Drosophila; C500957:rump protein, Drosophila