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

Hessle, Viktoria; Björk, Petra; Sokolowski, Marcus; González de Valdivia, Ernesto LU ; Silverstein, Rebecca; Artemenko, Konstantin; Tyagi, Anu; Maddalo, Gianluca; Ilag, Leopold and Helbig, Roger, et al. (2009) In Molecular Biology of the Cell 20(15). p.70-3459
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.... (More)

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.

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@article{18431fda-9df4-42e7-b573-6eea358cabb2,
  abstract     = {<p>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.</p>},
  author       = {Hessle, Viktoria and Björk, Petra and Sokolowski, Marcus and González de Valdivia, Ernesto and Silverstein, Rebecca and Artemenko, Konstantin and Tyagi, Anu and Maddalo, Gianluca and Ilag, Leopold and Helbig, Roger and Zubarev, Roman A and Visa, Neus},
  issn         = {1939-4586},
  keyword      = {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},
  language     = {eng},
  number       = {15},
  pages        = {70--3459},
  publisher    = {American Society for Cell Biology},
  series       = {Molecular Biology of the Cell},
  title        = {The exosome associates cotranscriptionally with the nascent pre-mRNP through interactions with heterogeneous nuclear ribonucleoproteins},
  url          = {http://dx.doi.org/10.1091/mbc.E09-01-0079},
  volume       = {20},
  year         = {2009},
}