Helicase-dependent RNA decay illuminated by a cryo-EM structure of a human nuclear RNA exosome-MTR4 complex Journal Article


Authors: Weick, E. M.; Puno, M. R.; Januszyk, K.; Zinder, J. C.; DiMattia, M. A.; Lima, C. D.
Article Title: Helicase-dependent RNA decay illuminated by a cryo-EM structure of a human nuclear RNA exosome-MTR4 complex
Abstract: The ribonucleolytic RNA exosome interacts with RNA helicases to degrade RNA. To understand how the 3′ to 5′ Mtr4 helicase engages RNA and the nuclear exosome, we reconstituted 14-subunit Mtr4-containing RNA exosomes from Saccharomyces cerevisiae, Schizosaccharomyces pombe, and human and show that they unwind structured substrates to promote degradation. We loaded a human exosome with an optimized DNA-RNA chimera that stalls MTR4 during unwinding and determined its structure to an overall resolution of 3.45 Å by cryoelectron microscopy (cryo-EM). The structure reveals an RNA-engaged helicase atop the non-catalytic core, with RNA captured within the central channel and DIS3 exoribonuclease active site. MPP6 tethers MTR4 to the exosome through contacts to the RecA domains of MTR4. EXOSC10 remains bound to the core, but its catalytic module and cofactor C1D are displaced by RNA-engaged MTR4. Competition for the exosome core may ensure that RNA is committed to degradation by DIS3 when engaged by MTR4. The cryo-EM structure of the human nuclear exosome-Mtr4 complex loaded with an RNA substrate reveals mechanistic insights to how the helicase unwinds structured RNA substrates to promote degradation. © 2018 Elsevier Inc.
Keywords: helicase; rna degradation; ribonuclease; nuclear; exosome; hydrolase; translocase; exoribonuclease; rna-protein complex; sf2
Journal Title: Cell
Volume: 173
Issue: 7
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2018-06-14
Start Page: 1663
End Page: 1677.e21
Language: English
DOI: 10.1016/j.cell.2018.05.041
PROVIDER: scopus
PUBMED: 29906447
DOI/URL:
Notes: Article -- Export Date: 2 July 2018 -- Source: Scopus
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MSK Authors
  1. Christopher D Lima
    83 Lima
  2. John C Zinder
    5 Zinder
  3. Marc Rhyan Jimenez Puno
    3 Puno
  4. Eva-Maria Weick
    1 Weick