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

TY - JOUR

T1 - The exosome associates cotranscriptionally with the nascent pre-mRNP through interactions with heterogeneous nuclear ribonucleoproteins

AU - Hessle, Viktoria

AU - Björk, Petra

AU - Sokolowski, Marcus

AU - Gonzalez de Valdivia, Ernesto I

AU - Silverstein, Rebecca

AU - Artemenko, Konstantin

AU - Tyagi, Anu

AU - Maddalo, Gianluca

AU - Ilag, Leopold

AU - Helbig, Roger

AU - Zubarev, Roman A

AU - Visa, Neus

PY - 2009/8/1

Y1 - 2009/8/1

N2 - 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.

AB - 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.

KW - Animals

KW - Blotting, Western

KW - Cell Line

KW - Cells, Cultured

KW - Chironomidae

KW - Chromosomes

KW - Drosophila Proteins

KW - Drosophila melanogaster

KW - Exosomes

KW - Heterogeneous-Nuclear Ribonucleoproteins

KW - Immunoprecipitation

KW - Microscopy, Confocal

KW - Microscopy, Immunoelectron

KW - Protein Binding

KW - Protein Precursors

KW - RNA Interference

KW - RNA-Binding Proteins

KW - Ribonucleoproteins

KW - Transcription, Genetic

U2 - 10.1091/mbc.E09-01-0079

DO - 10.1091/mbc.E09-01-0079

M3 - Journal article

C2 - 19494042

SN - 1059-1524

VL - 20

SP - 3459

EP - 3470

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

IS - 15

ER -