The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities

Schaeffer, Daneen; Tsanova, Borislava; Barbas, Ana; Reis, Filipa P.; Dastidar, Eeshita G; Sanchez-Rotunno, Maya; Arraiano, Cecília M.; Hoof, Ambro van

doi:10.1038/nsmb.1528

Cited by 272 publications

(338 citation statements)

References 58 publications

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“…In addition, the N terminus of Rrp44p contains an endonucleolytic PIN domain. Either active site is sufficient for viability; however, simultaneous inactivation of both nuclease activities results in a lack of cell growth (11)(12)(13). Although the biological substrates of the Rrp44p endonuclease have not been fully elucidated, the synthetic lethality observed upon inactivation of the Rrp44p nucleases implies that they have overlapping functions.…”

Section: Dis3 | Saccharomyces Cerevisiaementioning

confidence: 99%

Different nuclease requirements for exosome-mediated degradation of normal and nonstop mRNAs

Schaeffer

Hoof

2011

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

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Two general pathways of mRNA decay have been characterized in yeast. In one pathway, the mRNA is degraded by the cytoplasmic form of the exosome. The exosome has both 3′ to 5′ exoribonuclease and endoribonuclease activity, and the available evidence suggests that the exonuclease activity is required for the degradation of mRNAs. We confirm here that this is true for normal mRNAs, but that aberrant mRNAs that lack a stop codon can be efficiently degraded in the absence of the exonuclease activity of the exosome. Specifically, we show that the endo-and exonuclease activities of the exosome are both capable of rapidly degrading nonstop mRNAs and ribozyme-cleaved mRNAs. Additionally, the endonuclease activity of the exosome is not required for endonucleolytic cleavage in no-go decay. In vitro, the endonuclease domain of the exosome is active only under nonphysiological conditions, but our findings show that the in vivo activity is sufficient for the rapid degradation of nonstop mRNAs. Thus, whereas normal mRNAs are degraded by two exonucleases (Xrn1p and Rrp44p), several endonucleases contribute to the decay of many aberrant mRNAs, including transcripts subject to nonstop and nogo decay. Our findings suggest that the nuclease requirements for general and nonstop mRNA decay are different, and describe a molecular function of the core exosome that is not disrupted by inactivating its exonuclease activity.Dis3 | Saccharomyces cerevisiae

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Section: Dis3 | Saccharomyces Cerevisiaementioning

confidence: 99%

Different nuclease requirements for exosome-mediated degradation of normal and nonstop mRNAs

Schaeffer

Hoof

2011

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

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“…The sole RNase activity of the eukaryotic exosome comes from the tenth protein, npg www.cell-research.com | Cell Research Rrp44 (Dis3), which attaches to the bottom of the core complex. Rrp44 is a multi-domain protein with a processive hydrolytic exonuclease activity at its C-terminal region, which is homologous to bacterial RNase II, and a relatively weak endonuclease activity at its N-terminal region [10][11][12]. Previous structural studies have shown that Rrp44 specifically interacts with Rrp41, Rrp43 and Rrp45 of the core complex, aligning with the central channel's exit of the core complex [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

CryoEM structure of yeast cytoplasmic exosome complex

Liu

Niu

et al. 2016

Cell Res

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The eukaryotic multi-subunit RNA exosome complex plays crucial roles in 3′-to-5′ RNA processing and decay. Rrp6 and Ski7 are the major cofactors for the nuclear and cytoplasmic exosomes, respectively. In the cytoplasm, Ski7 helps the exosome to target mRNAs for degradation and turnover via a through-core pathway. However, the interaction between Ski7 and the exosome complex has remained unclear. The transaction of RNA substrates within the exosome is also elusive. In this work, we used single-particle cryo-electron microscopy to solve the structures of the Ski7-exosome complex in RNA-free and RNA-bound forms at resolutions of 4.2 Å and 5.8 Å, respectively. These structures reveal that the N-terminal domain of Ski7 adopts a structural arrangement and interacts with the exosome in a similar fashion to the C-terminal domain of nuclear Rrp6. Further structural analysis of exosomes with RNA substrates harboring 3′ overhangs of different length suggests a switch mechanism of RNA-induced exosome activation in the through-core pathway of RNA processing.

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“…Both of these minimal exosomes are able to interact with the catalytic subunit and rNa. it has been proposed previously that more than one conformation of the exosome exists in fly cells (andrulis et al, 2002) and that some mutations in yeast csl4 disrupt only specific exosome functions (Schaeffer et al, 2009;van Hoof et al, 2000), which is con sistent with the existence of multiple forms of the exosome. Whether the seven mer and eight mer minimal exosomes described by the Lorentzen group are formed and function in vivo remains to be determined.…”

Section: Flexibility Within the Exosomementioning

confidence: 98%