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Nuclear RNA surveillance: role of TRAMP in controlling exosome specificity
Author(s) -
Schmidt Karyn,
Butler J. Scott
Publication year - 2013
Publication title -
wiley interdisciplinary reviews: rna
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.225
H-Index - 71
eISSN - 1757-7012
pISSN - 1757-7004
DOI - 10.1002/wrna.1155
Subject(s) - exosome complex , rna , tramp , biology , polyadenylation , microbiology and biotechnology , non coding rna , exosome , computational biology , genetics , gene , microrna , microvesicles , transgene
The advent of high‐throughput sequencing technologies has revealed that pervasive transcription generates RNAs from nearly all regions of eukaryotic genomes. Normally, these transcripts undergo rapid degradation by a nuclear RNA surveillance system primarily featuring the RNA exosome. This multimeric protein complex plays a critical role in the efficient turnover and processing of a vast array of RNAs in the nucleus. Despite its initial discovery over a decade ago, important questions remain concerning the mechanisms that recruit and activate the nuclear exosome. Specificity and modulation of exosome activity requires additional protein cofactors, including the conserved TRAMP polyadenylation complex. Recent studies suggest that helicase and RNA‐binding subunits of TRAMP direct RNA substrates for polyadenylation, which enhances their degradation by Dis3/Rrp44 and Rrp6, the two exosome‐associated ribonucleases. These findings indicate that the exosome and TRAMP have evolved highly flexible functions that allow recognition of a wide range of RNA substrates. This flexibility provides the nuclear RNA surveillance system with the ability to regulate the levels of a broad range of coding and noncoding RNAs, which results in profound effects on gene expression, cellular development, gene silencing, and heterochromatin formation. This review summarizes recent findings on the nuclear RNA surveillance complexes, and speculates upon possible mechanisms for TRAMP‐mediated substrate recognition and exosome activation. WIREs RNA 2013, 4:217–231. doi: 10.1002/wrna.1155 This article is categorized under: RNA Processing > 3' End Processing RNA Processing > Processing of Small RNAs RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms

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