Reconstitution, Activities, and Structure of the Eukaryotic RNA Exosome

Liu, Quansheng; Greimann, Jaclyn C.; Lima, Christopher D.

doi:10.1016/j.cell.2007.09.019

Cited by 118 publications

(285 citation statements)

References 2 publications

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“…While this paper was under review, we learned that, similar to the yeast core exosome, the human core exosome is not enzymatically active (43). This observation seems to futher strengthen our prediction that the RE architecture and its RNA degradation mechanism are conserved across eukaryotes.…”

Section: Docking Of the Atomic Model Em Map Alignment And Sequencesupporting

confidence: 52%

Architecture of the yeast Rrp44–exosome complex suggests routes of RNA recruitment for 3′ end processing

Wang

Ding

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The eukaryotic core exosome (CE) is a conserved nine-subunit protein complex important for 3 end trimming and degradation of RNA. In yeast, the Rrp44 protein constitutively associates with the CE and provides the sole source of processive 3-to-5 exoribonuclease activity. Here we present EM reconstructions of the core and Rrp44-bound exosome complexes. The two-lobed Rrp44 protein binds to the RNase PH domain side of the exosome and buttresses the bottom of the exosome-processing chamber. The Rrp44 C-terminal body part containing an RNase II-type active site is anchored to the exosome through a conserved set of interactions mainly to the Rrp45 and Rrp43 subunit, whereas the Rrp44 Nterminal head part is anchored to the Rrp41 subunit and may function as a roadblock to restrict access of RNA to the active site in the body region. The Rrp44 -exosome (RE) architecture suggests an active site sequestration mechanism for strict control of 3 exoribonuclease activity in the RE complex.electron microscopy ͉ single-particle reconstruction ͉ exoribonuclease

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Section: Docking Of the Atomic Model Em Map Alignment And Sequencesupporting

confidence: 52%

Architecture of the yeast Rrp44–exosome complex suggests routes of RNA recruitment for 3′ end processing

Wang

Ding

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…The tenth subunit, Dis3p (also known as Rrp44), is homologous to a bacterial RNase II that is a hydrolytic 3′ to 5′ exoribonuclease (Mitchell et al 1997;Allmang et al 1999). Structural and functional analysis revealed that Dis3p is the only subunit responsible for the hydrolytic 3′ to 5′ exonucleolytic activity of the exosome core (Liu et al 2006;Dziembowski et al 2007). Moreover, this subunit also has recently been shown to contain endonuclease activity that is of functional consequence in vivo (Lebreton et al 2008;Schaeffer et al 2009).…”

Section: ′ To 5′ Exoribonucleasesmentioning

confidence: 99%

“…Moreover, this subunit also has recently been shown to contain endonuclease activity that is of functional consequence in vivo (Lebreton et al 2008;Schaeffer et al 2009). Other subunits do not have enzymatic activity, but are required for the interaction of associated proteins with Dis3p (Liu et al 2006;Dziembowski et al 2007). In the nucleus, the exosome is involved in the processing of rRNA, snoRNA, and snRNA.…”

Section: ′ To 5′ Exoribonucleasesmentioning

confidence: 99%

“…There are two genes that may encode the Dis3p homolog in the Arabidopsis genome, suggesting that the exosome composition may differ between yeast and multicellular eukaryotes (Chekanova et al 2007). In fact, the Dis3p homologue in humans does not seem to be associated stably with the exosome complex, although the rest of the components appear to be quite similar to yeast (Allmang et al 1999;Raijmakers et al 2004;Liu et al 2006). Additionally, AtRRP41 is unique in that it retains the full catalytic activity (Chekanova et al 2000).…”

Section: ′ To 5′ Exoribonucleasesmentioning

confidence: 99%

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mRNA Degradation Machinery in Plants

Chiba

Green

2009

J. Plant Biol.

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Control of gene expression is exerted by multiple steps such as transcription, mRNA processing, mRNA export, mRNA degradation, translation, and posttranslational events. Recent discovery of small RNAs has enhanced the impact of posttranscriptional regulation, in particular, alterations in mRNA stability in the regulation of gene expression. Therefore, mRNA turnover is an important process not only for setting the basal level of gene expression but also as a regulatory step. Compared to the mechanism of transcription, much less information is available regarding mRNA degradation machineries. However, in the past several years, various components involved in the mRNA degradation process have been identified in eukaryotes. In particular, progress in the plant field has revealed the involvement of mRNA turnover in a wide variety of developmental processes and hormonal responses. Here, we provide an overview of machineries involved in general mRNA degradation and mRNA surveillance systems in plants.

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“…The structure of the human exosome PNPase-like core reported recently revealed an architecture very similar to the archaeal complex (26). Although phosphorolytic activity has been observed for some isolated subunits of the eukaryotic exosome (1, 27) and for the human heterodimer Rrp41/Rrp45 (26), recent studies have shown that only the hydrolytic exoribonucleases are active in the context of the eukaryotic complex (28,29). Although this loss of phosphorolytic activity may be related to a reduction in the selection pressure compensated by the presence of additional hydrolytic subunits (30), the eukaryotic exosome PNPase-core may on the other hand have assumed a role as scaffold for interaction with the proteins assisting its various activities (28).…”

mentioning

confidence: 99%

Insights into the Mechanism of Progressive RNA Degradation by the Archaeal Exosome

Navarro

Oliveira

Zanchin

et al. 2008

Journal of Biological Chemistry

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Initially identified in yeast, the exosome has emerged as a central component of the RNA maturation and degradation machinery both in Archaea and eukaryotes. Here we describe a series of high-resolution structures of the RNase PH ring from the Pyrococcus abyssi exosome, one of them containing three 10-mer RNA strands within the exosome catalytic chamber, and report additional nucleotide interactions involving positions N5 and N7. Residues from all three Rrp41-Rrp42 heterodimers interact with a single RNA molecule, providing evidence for the functional relevance of exosome ring-like assembly in RNA processivity. Furthermore, an ADP-bound structure showed a rearrangement of nucleotide interactions at site N1, suggesting a rationale for the elimination of nucleoside diphosphate after catalysis. In combination with RNA degradation assays performed with mutants of key amino acid residues, the structural data presented here provide support for a model of exosome-mediated RNA degradation that integrates the events involving catalytic cleavage, product elimination, and RNA translocation. Finally, comparisons between the archaeal and human exosome structures provide a possible explanation for the eukaryotic exosome inability to catalyze phosphate-dependent RNA degradation.Initially described as a multisubunit RNase complex required for maturation of 5.8 S rRNA in yeast (1), the 3Ј 3 5Ј exoribonuclease complex exosome was subsequently shown to play a central role on numerous pathways related to RNA processing and degradation, both in the nucleus and in the cytoplasm (reviewed in Ref. 2). These include 3Ј end processing of rRNAs, small nuclear RNAs, and small nucleolar RNAs (3-5), degradation of aberrant pre-mRNAs, pre-tRNAs, and pre-rRNAs (6 -9), normal turnover of cytosolic mRNAs (10), and degradation of RNA fragments produced during RNA interference processes (11, 12).Increasing structural and genetic studies with archaeal and eukaryotic exosomes have unveiled the evolutionary conservation of its molecular architecture (1, 13-18). The archaeal exosome consists of two RNase PH subunits (Rrp41 and Rrp42) and two proteins containing the S1/KH (Rrp4) or S1/zinc ribbon (Csl4) RNA-binding domains (17)(18)(19). Determination of the three-dimensional structure of the Sulfolobus solfataricus and Archaeoglobus fulgidus exosomes revealed a PNPase-like fold (20), composed by alternating RNase PH subunits assembled into a hexameric ring capped by a trimer of RNA-binding proteins, which can be formed by either Rrp4 or Csl4 or possibly by a mixture of both (19,21,22). Such an architecture encloses the exoribonucleolytic active sites at the bottom of the RNase PH ring catalytic chamber and restricts the entry to only unstructured RNA through the S1 pore, formed by the RNAbinding subunits of the exosome cap placed at the top of the ring (19,(21)(22)(23). Both Rrp41 and Rrp42 subunits possess the same RNase PH-fold and are involved in substrate binding, but the amino acid residues contributing to the interactions with the phosphate nucle...

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Reconstitution, Activities, and Structure of the Eukaryotic RNA Exosome

Cited by 118 publications

References 2 publications

Architecture of the yeast Rrp44–exosome complex suggests routes of RNA recruitment for 3′ end processing

Architecture of the yeast Rrp44–exosome complex suggests routes of RNA recruitment for 3′ end processing

mRNA Degradation Machinery in Plants

Insights into the Mechanism of Progressive RNA Degradation by the Archaeal Exosome

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