Mechanisms of RNA Degradation by the Eukaryotic Exosome

Tomecki, Rafał; Drążkowska, Karolina; Dziembowski, Andrzej

doi:10.1002/cbic.201000025

Cited by 36 publications

(40 citation statements)

References 88 publications

(130 reference statements)

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“…Two active subunits, Rrp6 and Rrp44/Dis3, were identified initially in budding yeast and are conserved in higher eukaryotes (Mitchell et al 1997;Andrulis et al 2002). A third active subunit, Dis3L, has recently been identified in human cells (Staals et al 2010;Tomecki et al 2010). There is ample evidence for the functional association of the catalytic subunits with the core of the exosome in both yeast and metazoans (Andrulis et al 2002;Synowsky et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Rrp6 is recruited to transcribed genes and accompanies the spliced mRNA to the nuclear pore

Hessle

Euler²,

Valdivia

et al. 2012

RNA

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Rrp6 is an exoribonuclease involved in the quality control of mRNA biogenesis. We have analyzed the association of Rrp6 with the Balbiani ring pre-mRNPs of Chironomus tentans to obtain insight into the role of Rrp6 in splicing surveillance. Rrp6 is recruited to transcribed genes and its distribution along the genes does not correlate with the positions of exons and introns. In the nucleoplasm, Rrp6 is bound to both unspliced and spliced transcripts. Rrp6 is released from the mRNPs in the vicinity of the nuclear pore before nucleo-cytoplasmic translocation. We show that Rrp6 is associated with newly synthesized transcripts during all the nuclear steps of gene expression and is associated with the transcripts independently of their splicing status. These observations suggest that the quality control of pre-mRNA splicing is not based on the selective recruitment of the exoribonuclease Rrp6 to unprocessed mRNAs.

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Section: Introductionmentioning

confidence: 99%

Rrp6 is recruited to transcribed genes and accompanies the spliced mRNA to the nuclear pore

Hessle

Euler²,

Valdivia

et al. 2012

RNA

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“…Dis3 also harbors an N-terminal PilT N terminus (PIN) domain that possesses RNA endonuclease activity (Lebreton et al 2008). Dis3 appears to act as the principle catalytic subunit of the RNA exosome, a large multisubunit protein complex that can degrade and/or process all classes of RNA (Kinoshita et al 1991;Mitchell et al 1997;Dziembowski et al 2007; Lebreton et al 2008;Tomecki et al 2010). Emerging work indicates that noncoding RNAs and RNA processing enzymes, like the RNA exosome, regulate centromere and kinetochore formation and function (Volpe et al 2002;Topp et al 2004;Verdel et al 2004;Buhler et al 2007;Murakami et al 2007;Wong et al 2007;Folco et al 2008;Chan et al 2012;Rosic et al 2014).…”

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confidence: 99%

Collaborative Control of Cell Cycle Progression by the RNA Exonuclease Dis3 and Ras Is Conserved Across Species

et al. 2016

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Dis3 encodes a conserved RNase that degrades or processes all RNA species via an N-terminal PilT N terminus (PIN) domain and C-terminal RNB domain that harbor, respectively, endonuclease activity and 39-59 exonuclease activity. In Schizosaccharomyces pombe, dis3 mutations cause chromosome missegregation and failure in mitosis, suggesting dis3 promotes cell division. In humans, apparently hypomorphic dis3 mutations are found recurrently in multiple myeloma, suggesting dis3 opposes cell division. Except for the observation that RNAi-mediated depletion of dis3 function drives larval arrest and reduces tissue growth in Drosophila, the role of dis3 has not been rigorously explored in higher eukaryotic systems. Using the Drosophila system and newly generated dis3 null alleles, we find that absence of dis3 activity inhibits cell division. We uncover a conserved CDK1 phosphorylation site that when phosphorylated inhibits Dis3's exonuclease, but not endonuclease, activity. Leveraging this information, we show that Dis3's exonuclease function is required for mitotic cell division: in its absence, cells are delayed in mitosis and exhibit aneuploidy and overcondensed chromosomes. In contrast, we find that modest reduction of dis3 function enhances cell proliferation in the presence of elevated Ras activity, apparently by accelerating cells through G2/M even though each insult by itself delays G2/M. Additionally, we find that dis3 and ras genetically interact in worms and that dis3 can enhance cell proliferation under growth stimulatory conditions in murine B cells. Thus, reduction, but not absence, of dis3 activity can enhance cell proliferation in higher organisms.

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“…Degradation of nonfunctional mRNA is mediated by conserved nucleases, which digest mRNA from either the 5= or the 3= end (5,14,28,51). Depending on the type of defect within the mRNA, recognition involves different surveillance machineries.…”

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confidence: 99%

Ribosome-Associated Complex and Ssb Are Required for Translational Repression Induced by Polylysine Segments within Nascent Chains

Chiabudini

Conz

Reckmann

et al. 2012

Molecular and Cellular Biology

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bWhen a polyadenylated nonstop transcript is fully translated, a complex consisting of the ribosome, the nonstop mRNA, and the C-terminally polylysine-tagged protein is generated. In Saccharomyces cerevisiae, a 3-step quality control system prevents formation of such dead-end complexes. Nonstop mRNA is rapidly degraded, translation of nonstop mRNA is repressed, and finally, nonstop proteins are cotranslationally degraded. Nonstop mRNA degradation depends on Ski7 and the exosome; nonstop protein degradation depends on the ribosome-bound E3 ligase Ltn1 and the proteasome. However, components which mediate translational repression of nonstop mRNA have previously not been identified. Here we show that the ribosome-bound chaperone system consisting of the ribosome-associated complex (RAC) and the Hsp70 homolog Ssb is required to stabilize translationally repressed ribosome-polylysine protein complexes, without affecting the folding or the degradation of polylysine proteins. As a consequence, in the absence of RAC/Ssb, polylysine proteins escaped translational repression and subsequently folded into their native conformation. This active role of RAC/Ssb in the quality control of polylysine proteins significantly contributed to the low level of expression of nonstop transcripts in vivo.

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Mechanisms of RNA Degradation by the Eukaryotic Exosome

Cited by 36 publications

References 88 publications

Rrp6 is recruited to transcribed genes and accompanies the spliced mRNA to the nuclear pore

Rrp6 is recruited to transcribed genes and accompanies the spliced mRNA to the nuclear pore

Collaborative Control of Cell Cycle Progression by the RNA Exonuclease Dis3 and Ras Is Conserved Across Species

Ribosome-Associated Complex and Ssb Are Required for Translational Repression Induced by Polylysine Segments within Nascent Chains

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