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MBC in Press, published online ahead of print June 3, 2009
Mol. Biol. Cell 10.1091/mbc.E09-01-0079

A more recent version of this article appeared on August 1, 2009 Originally published as MBC in Press, 10.1091/mbc.E09-01-0079 on June 10, 2009
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Submitted on January 26, 2009
Revised on May 19, 2009
Accepted on May 21, 2009

The Exosome Associates Cotranscriptionally with the Nascent Pre-mRNP through Interactions with hnRNP Proteins

Viktoria Hessle,* Petra Björk,* Marcus Sokolowski,*{dagger} Ernesto González de Valdivia,* Rebecca Silverstein,* Konstantin Artemenko,{ddagger} Anu Tyagi,* Gianluca Maddalo,{sect} Leopold Ilag,{sect} Roger Helbig,* Roman A. Zubarev,{ddagger} and Neus Visa*

*Department of Molecular Biology and Functional Genomics, Stockholm University, SE-10 691 Stockholm, Sweden; {ddagger}Division of Molecular Biometry, Institute for Cell and Molecular Biology, Uppsala University, SE-75 124 Uppsala, Sweden; {sect}Department of Analytical Chemistry, Stockholm University, SE-10 691 Stockholm, Sweden

Monitoring Editor: Wendy Bickmore

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.

{dagger}Present address: Department of Public Health Sciences, Karolinska institutet, SE-17 177 Stockholm, Sweden.

Address correspondence to: Neus Visa (neus.visa{at}molbio.su.se)






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