Cited by 52RNA Research and SplicingNuclear Structure and FunctionRNA regulation and disease

Mpp6 Incorporation in the Nuclear Exosome Contributes to RNA Channeling through the Mtr4 Helicase

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Falk, Sebastian, Bonneau, Fabien, Ebert, Judith, Kögel, Alexander, Conti, Elena·2017·Cell Reports

Abstract

The RNA-degrading exosome mediates the processing and decay of many cellular transcripts. In the yeast nucleus, the ubiquitous 10-subunit exosome core complex (Exo-9-Rrp44) functions with four conserved cofactors (Rrp6, Rrp47, Mtr4, and Mpp6). Biochemical and structural studies to date have shed insights into the mechanisms of the exosome core and its nuclear cofactors, with the exception of Mpp6. We report the 3.2-Å resolution crystal structure of a S. cerevisiae Exo-9-Mpp6 complex, revealing how linear motifs in the Mpp6 middle domain bind Rrp40 via evolutionary conserved residues. In particular, Mpp6 binds near a tryptophan residue of Rrp40 that is mutated in human patients suffering from pontocerebellar hypoplasia. Using biochemical assays, we show that Mpp6 is required for the ability of Mtr4 to extend the trajectory of an RNA entering the exosome core, suggesting that it promotes the channeling of substrates from the nuclear helicase to the processive RNase.

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  • Catalytic activities of the RNA exosome are mediated by associated 3'−5' exonucleases EXOSC10 and DIS3 or accessory factors such as MTR4, while core components including EXOSC3 provide structural stability and facilitate substrate recognition and/or RNA threading.

    “The catalytic activities of the RNA exosome are mediated by associated 3’−5’ exonucleases EXOSC10 and DIS3 or accessory factors such as the RNA helicase MTR4, while core components including EXOSC3 provide structural stability and facilitate substrate recognition and/or RNA threading through the protein complex core39–43.”

    From EXOSC3 G191 Variants Trigger System-Wide Recalibration of RNA Processing Machinery (2026) · cites this paper as [41]

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Authors
Falk, S., Bonneau, F., Ebert, J., Kögel, A., & Conti, E.
Affiliations
Max Planck Society (DE)
Corresponding author
Conti, Elena
Venue
Cell Reports
Publisher
Elsevier BV
Published
2017-09
Volume
20
Issue
10
Pages
2279-2286
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2751092007
Cited by
52
References
28
Citations by year
2026: 3 · 2025: 6 · 2024: 2 · 2023: 7 · 2022: 5 · 2021: 8 · 2020: 3 · 2019: 8 · 2018: 8 · 2017: 2
FWCI
2.35
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DORA PSI (Paul Scherrer Institute) (submittedVersion, cc-by-nc-nd)
  • MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Max Planck Gesellschaft
  • European Research Council (294371)
  • Deutsche Forschungsgemeinschaft (SFB1035, GRK1721)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
MPP6, nuclear exosome, RNA degradation, pontocerebellar hypoplasia, crystal structure, Saccharomyces cerevisiae
MeSH terms
Cell Nucleus, Humans, Membrane Proteins, Ribosomes, RNA, Crystallography, X-Ray, RNA Helicases, Exosomes

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