The exosome associates cotranscriptionally with the nascent pre-mRNP through interactions with heterogeneous nuclear ribonucleoproteins

Research output: Contribution to journalArticle

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.

Details

Authors
  • Viktoria Hessle
  • Petra Björk
  • Marcus Sokolowski
  • Ernesto González de Valdivia
  • Rebecca Silverstein
  • Konstantin Artemenko
  • Anu Tyagi
  • Gianluca Maddalo
  • Leopold Ilag
  • Roger Helbig
  • Roman A Zubarev
  • Neus Visa
External organisations
  • Stockholm University
Research areas and keywords

Keywords

  • Animals, Blotting, Western, Cell Line, Cells, Cultured, Chironomidae, Chromosomes, Drosophila Proteins, Drosophila melanogaster, Exosomes, Heterogeneous-Nuclear Ribonucleoproteins, Immunoprecipitation, Microscopy, Confocal, Microscopy, Immunoelectron, Protein Binding, Protein Precursors, RNA Interference, RNA-Binding Proteins, Ribonucleoproteins, Transcription, Genetic, Journal Article, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)3459-70
Number of pages12
JournalMolecular Biology of the Cell
Volume20
Issue number15
Publication statusPublished - 2009 Aug
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes