Co-transcriptional recruitment of the RNA exosome cofactors Rrp47p, Mpp6p and two distinct TRAMP complexes assists the exonuclease Rrp6p in the targeting and degradation of an aberrant mRNP in yeast

Abstract : The co-transcriptional mRNA processing and packaging reactions that lead to the formation of export-competent mRNPs are under the surveillance of quality control steps. Aberrant mRNPs resulting from faulty events are retained in the nucleus with ensuing elimination of their mRNA component. The molecular mechanisms by which the surveillance system recognizes defective mRNPs and stimulates their destruction by the RNA degradation machinery are still not completely elucidated. Using an experimental approach in which mRNP formation in yeast is disturbed by the action of the bacterial Rho helicase, we have shown previously that the targeting of Rho-induced aberrant mRNPs is mediated by Rrp6p which is recruited co-transcriptionally in association with Nrd1p following Rho action. Here, we investigated the specific involvement in this quality control process of different cofactors associated with the nuclear RNA degradation machinery. We show that, in addition to the main hydrolytic action of the exonuclease Rrp6p, the cofactors Rrp47p and Mpp6p as well as the TRAMP components Trf4p, Trf5p and Air2p contribute significantly by stimulating the degradation process upon their co-transcriptional recruitment. Trf4p and Trf5p are apparently recruited in two distinct TRAMP complexes that both contain Air2p as component. Surprisingly, Rrp47p appears to play an important role in mutual protein stabilization with Rrp6p which highlights a close association between the two partners. Together, our results provide an integrated view of how different cofactors of the RNA degradation machinery cooperate to target and eliminate aberrant mRNPs.
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Submitted on : Friday, October 18, 2013 - 6:08:22 PM
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Igor Stuparevic, Christine Mosrin-Huaman, Nadège Hervouet-Coste, Mateja Remenaric, A. Rachid Rahmouni. Co-transcriptional recruitment of the RNA exosome cofactors Rrp47p, Mpp6p and two distinct TRAMP complexes assists the exonuclease Rrp6p in the targeting and degradation of an aberrant mRNP in yeast. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2013, ⟨10.1074/jbc.M113.491290⟩. ⟨hal-00874892⟩

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