Cited by 153RNA Research and SplicingRNA regulation and diseaseRNA and protein synthesis mechanisms

Helicase-Dependent RNA Decay Illuminated by a Cryo-EM Structure of a Human Nuclear RNA Exosome-MTR4 Complex

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Weick, Eva-Maria, Puno, M. Rhyan, Januszyk, Kurt, Zinder, John C., DiMattia, Michael A., Lima, Christopher D.·2018·Cell

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.

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Crossref · 10.1016/j.cell.2018.05.041

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  • EXOSC3 p.G191 is located at a key structural position at the end of the S1-domain just prior to a linker region in front of the KH-type RNA-binding domain.

    “EXOSC3 p.G191 is located at a key structural position at the end of the S1-domain just prior to a linker region in front of the KH-type RNA-binding domain52.”

    From EXOSC3 G191 Variants Trigger System-Wide Recalibration of RNA Processing Machinery (2026) · cites this paper as [52]

    The Results section, “The MTR4 helicase is tethered to the exosome via EXOSC2 and MPP6” (page unavailable), identifies EXOSC3 Gly191 near the MPP6 Arg74 anchor, supporting its structural relevance. It does not locate Gly191 at the end of the S1 domain or place it before a linker and KH-type RNA-binding domain. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Previously reported structural analysis of the RNA exosome containing MTR4 and MPP6 revealed the close association of MPP6 with EXOSC3 in the cryo-EM human complex.

    “Previously reported structural analysis of the RNA exosome containing both the RNA helicase MTR4 and the RNA binding protein MPP6 revealed the close association of MPP6 with EXOSC3 in the cryo-EM human complex (Fig. 6B&C, 52).”

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Authors
Weick, E.-M., Puno, M. R., Januszyk, K., Zinder, J. C., DiMattia, M. A., & Lima, C. D.
Affiliations
Memorial Sloan Kettering Cancer Center (US)
Corresponding author
Lima, Christopher D.
Venue
Cell
Publisher
Elsevier BV
Published
2018-06
Volume
173
Issue
7
Pages
1663-1677.e21
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2808298553
Cited by
153
References
81
Citations by year
2026: 20 · 2025: 17 · 2024: 14 · 2023: 19 · 2022: 17 · 2021: 20 · 2020: 20 · 2019: 22 · 2018: 4
FWCI
5.87
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Simons Foundation (SF349247)
  • NYSTAR
  • NIH NIGMS (GM103310)
  • Agouron Institute (F00316)
  • NIH (S10 OD019994-01)
  • National Institute of General Medical Sciences of the NIH (R01GM079196, R35GM118080)
  • NIH-NCI-Cancer Center (P30 CA008748)
  • Human Frontier Science Program
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
RNA exosome, RNA degradation, MPP6, RNA unwinding, Saccharomyces cerevisiae, Schizosaccharomyces pombe
MeSH terms
DNA, DNA Helicases, Exoribonucleases, Humans, Image Processing, Computer-Assisted, Membrane Proteins, Protein Binding, RNA, Saccharomyces cerevisiae, Schizosaccharomyces, Substrate Specificity, Catalytic Domain, Cryoelectron Microscopy, RNA Helicases, Protein Structure, Quaternary, RNA Stability, Saccharomyces cerevisiae Proteins, Schizosaccharomyces pombe Proteins, Exosome Multienzyme Ribonuclease Complex

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