Mpp6 Incorporation in the Nuclear Exosome Contributes to RNA Channeling through the Mtr4 Helicase
Open accessAbstract
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)
- PMC
- PMC5603729
- 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
- gold
- doi.org
- Licence
- 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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