Extensive Degradation of RNA Precursors by the Exosome in Wild-Type Cells

Gudipati, Rajani Kanth; Xu, Zhenyu; Lebreton, Alice; Séraphin, Bertrand; Steinmetz, Lars M.; Jacquier, Alain; Libri, Domenico

doi:10.1016/j.molcel.2012.08.018

Cited by 218 publications

(292 citation statements)

References 59 publications

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“…tRNA Turnover and Cleavage tRNAs are stable with half-lives estimated to be from 9 hr to up to days (Anderson et al 1998;Phizicky and Hopper 2010;Gudipati et al 2012). So it is surprising that two separate pathways for tRNA turnover have been discovered (reviewed in Phizicky and Hopper 2010;Maraia and Lamichhane 2011;Parker 2012;Wolin et al 2012).…”

Section: Removal Of 59 Leader and 39 Trailer Sequences From Pre-trnasmentioning

confidence: 99%

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Transfer RNA Post-Transcriptional Processing, Turnover, and Subcellular Dynamics in the YeastSaccharomyces cerevisiae

2013

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Transfer RNAs (tRNAs) are essential for protein synthesis. In eukaryotes, tRNA biosynthesis employs a specialized RNA polymerase that generates initial transcripts that must be subsequently altered via a multitude of post-transcriptional steps before the tRNAs beome mature molecules that function in protein synthesis. Genetic, genomic, biochemical, and cell biological approaches possible in the powerful Saccharomyces cerevisiae system have led to exciting advances in our understandings of tRNA post-transcriptional processing as well as to novel insights into tRNA turnover and tRNA subcellular dynamics. tRNA processing steps include removal of transcribed leader and trailer sequences, addition of CCA to the 39 mature sequence and, for tRNA His , addition of a 59 G. About 20% of yeast tRNAs are encoded by intron-containing genes. The three-step splicing process to remove the introns surprisingly occurs in the cytoplasm in yeast and each of the splicing enzymes appears to moonlight in functions in addition to tRNA splicing. There are 25 different nucleoside modifications that are added post-transcriptionally, creating tRNAs in which 15% of the residues are nucleosides other than A, G, U, or C. These modified nucleosides serve numerous important functions including tRNA discrimination, translation fidelity, and tRNA quality control. Mature tRNAs are very stable, but nevertheless yeast cells possess multiple pathways to degrade inappropriately processed or folded tRNAs. Mature tRNAs are also dynamic in cells, moving from the cytoplasm to the nucleus and back again to the cytoplasm; the mechanism and function of this retrograde process is poorly understood. Here, the state of knowledge for tRNA post-transcriptional processing, turnover, and subcellular dynamics is addressed, highlighting the questions that remain. TABLE OF CONTENTS Abstract 43Introduction 44

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Section: Removal Of 59 Leader and 39 Trailer Sequences From Pre-trnasmentioning

confidence: 99%

“…Thus, this 39 to 59 turnover machinery likely serves as a quality control pathway that monitors both appropriate tRNA nuclear modification as well as 39 end maturation. Recent genome-wide studies indicate that as much as 50% of pre-tRNAs may be rapidly degraded by the exosome (Gudipati et al 2012). …”

Section: -59 Exonucleolytic Degradation By the Nuclear Exosomementioning

confidence: 99%

Transfer RNA Post-Transcriptional Processing, Turnover, and Subcellular Dynamics in the YeastSaccharomyces cerevisiae

2013

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“…Hence, they are restrained at the transcription site or the proximity of the nuclear pore, and eventually degraded in the nucleus (Jackson et al, 2000). Moreover, recent studies focusing on exosome targets in transcriptome revealed that massive amounts of RNA precursors are degraded before they enter functional pathways in Saccharomyces cerevisiae (Gudipati et al, 2012;Schneider et al, 2012). All of these observations announced the presence of extensive nuclear RNA degradation in eukaryotic cells.…”

Section: Introductionmentioning

confidence: 99%

mRNA stability in the nucleus

Liu

Luo

Wen

2014

J. Zhejiang Univ. Sci. B

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Abstract:Eukaryotic gene expression is controlled by different levels of biological events, such as transcription factors regulating the timing and strength of transcripts production, alteration of transcription rate by RNA processing, and mRNA stability during RNA processing and translation. RNAs, especially mRNAs, are relatively vulnerable molecules in living cells for ribonucleases (RNases). The maintenance of quality and quantity of transcripts is a key issue for many biological processes. Extensive studies draw the conclusion that the stability of RNAs is dedicated-regulated, occurring co-and post-transcriptionally, and translation-coupled as well, either in the nucleus or cytoplasm. Recently, RNA stability in the nucleus has aroused much research interest, especially the stability of newly-made transcripts. In this article, we summarize recent progresses on mRNA stability in the nucleus, especially focusing on quality control of newly-made RNA by RNA polymerase II in eukaryotes.

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“…Furthermore, both mRNAs and noncoding RNAs are subjected to quality control systems that eliminate incorrectly processed transcripts or misassembled ribonucleoprotein particles (Houseley and Tollervey 2009;Wolin et al 2012). A significant proportion of transcripts are degraded by such "RNA surveillance" processes, even in normally growing, healthy cells (Gudipati et al 2012). Finally, low level antisense and inter-genic transcription generates a large number of noncoding RNAs, many of which are subjected to rapid degradation (Wyers et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Rrp47 functions in RNA surveillance and stable RNA processing when divorced from the exoribonuclease and exosome-binding domains of Rrp6

Garland

Feigenbutz

Turner

et al. 2013

RNA

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The eukaryotic exosome exoribonuclease Rrp6 forms a complex with Rrp47 that functions in nuclear RNA quality control mechanisms, the degradation of cryptic unstable transcripts (CUTs), and in the 3 ′ end maturation of stable RNAs. Stable expression of Rrp47 is dependent upon its interaction with the N-terminal domain of Rrp6 (Rrp6 NT ). To address the function of Rrp47 independently of Rrp6, we developed a DECOID (decreased expression of complexes by overexpression of interacting domains) strategy to resolve the Rrp6/Rrp47 complex in vivo and employed mpp6Δ and rex1Δ mutants that are synthetic lethal with loss-of-function rrp47 mutants. Strikingly, Rrp47 was able to function in mpp6Δ and rex1Δ mutants when separated from the catalytic and exosome-binding domains of Rrp6, whereas a truncated Rrp47 protein lacking its C-terminal region caused a block in cell growth. Northern analyses of the conditional mutants revealed a specific block in the 3 ′ maturation of box C/D snoRNAs in the rex1 rrp47 mutant and widespread inhibition of Rrp6-mediated RNA surveillance processes in the mpp6 rrp47 mutant. In contrast, growth analyses and RNA northern blot hybridization analyses showed no effect on the rrp47Δ mutant upon overexpression of the Rrp6 NT domain. These findings demonstrate that Rrp47 and Rrp6 have resolvable functions in Rrp6-mediated RNA surveillance and processing pathways. In addition, this study reveals a redundant requirement for Rrp6 or Rex1 in snoRNA maturation and demonstrates the effective use of the DECOID strategy for the resolution and functional analysis of protein complexes.

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Extensive Degradation of RNA Precursors by the Exosome in Wild-Type Cells

Cited by 218 publications

References 59 publications

Transfer RNA Post-Transcriptional Processing, Turnover, and Subcellular Dynamics in the YeastSaccharomyces cerevisiae

Transfer RNA Post-Transcriptional Processing, Turnover, and Subcellular Dynamics in the YeastSaccharomyces cerevisiae

mRNA stability in the nucleus

Rrp47 functions in RNA surveillance and stable RNA processing when divorced from the exoribonuclease and exosome-binding domains of Rrp6

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