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

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  • Viktoria Hessle
  • Petra Björk
  • Marcus Sokolowski
  • Ernesto I Gonzalez de Valdivia
  • Rebecca Silverstein
  • Konstantin Artemenko
  • Anu Tyagi
  • Gianluca Maddalo
  • Leopold Ilag
  • Roger Helbig
  • Roman A Zubarev
  • Neus Visa
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.
OriginalsprogEngelsk
TidsskriftMolecular Biology of the Cell
Vol/bind20
Udgave nummer15
Sider (fra-til)3459-70
Antal sider12
ISSN1059-1524
DOI
StatusUdgivet - 1 aug. 2009

ID: 32642020