engleski

THE ROLE OF Rrp6 COFACTORS IN mRNP BIOGENESIS AND QUALITY CONTROL

During transcription elongation in the eukaryotic nucleus, the nascent mRNA molecule is sequentially coated with a variety of proteins that mediate its transformation into an export-competent ribonucleoprotein particle (mRNP) ready for translation. The co- transcriptional maturation and assembly of export-competent mRNPs is facilitated by C- terminal domain (CTD) of RNA polymerase II (RNAP II) that serves as a platform for sequential recruitment of the various factors. The production of export-competent transcripts is under the surveillance of quality control steps that are interconnected with transcription elongation and mRNP biogenesis. However, linkage and coordination between transcription and these co-transcriptional processes remain largely unknown and its study is one of the major challenges of the next decade to understand the cellular dysfunctions at the origin of many genetic diseases as well as cancer. Using an experimental approach in which mRNP formation in yeast is disturbed by the action of the bacterial Rho helicase, we have shown that the targeting of Rho-induced aberrant mRNPs is mediated by Rrp6p, which is recruited cotranscriptionally in association with Nrd1p following Rho action. We show that, in addition to the main hydrolytic action of the exonuclease Rrp6p, the cofactors Rrp47p, Mpp6p as well as the Trf-Air-Mtr4 polyadenylation (TRAMP) components Trf4p, Trf5p, and Air2p contribute significantly by stimulating the degradation process upon their cotranscriptional 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.

Rrp6, Rrp6 cofactors, mRNP

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