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Cited by 60RNA Research and SplicingRNA regulation and diseaseRNA and protein synthesis mechanisms

The RNA exosome complex central channel controls both exonuclease and endonuclease Dis3 activities in vivo and in vitro

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Drążkowska, Karolina, Tomecki, Rafał, Stoduś, Krystian, Kowalska, Katarzyna, Czarnocki-Cieciura, Mariusz, Dziembowski, Andrzej·2013·Nucleic Acids Research
DOI 10.1093/nar/gkt060PMC PMC3616716
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Abstract

The RNA exosome is an essential ribonuclease complex involved in RNA processing and decay. It consists of a 9-subunit catalytically inert ring composed of six RNase PH-like proteins forming a central channel and three cap subunits with KH/S1 domains located at the top. The yeast exosome catalytic activity is supplied by the Dis3 (also known as Rrp44) protein, which has both endo- and exoribonucleolytic activities and the nucleus-specific exonuclease Rrp6. In vitro studies suggest that substrates reach the Dis3 exonucleolytic active site following passage through the ring channel, but in vivo support is lacking. Here, we constructed an Rrp41 ring subunit mutant with a partially blocked channel that led to thermosensitivity and synthetic lethality with Rrp6 deletion. Rrp41 mutation caused accumulation of nuclear and cytoplasmic exosome substrates including the non-stop decay reporter, for which degradation is dependent on either endonucleolytic or exonucleolytic Dis3 activities. This suggests that the central channel also controls endonucleolytic activity. In vitro experiments performed using Chaetomium thermophilum exosomes reconstituted from recombinant subunits confirmed this notion. Finally, we analysed the impact of a lethal mutation of conserved basic residues in Rrp4 cap subunit and found that it inhibits digestion of single-stranded and structured RNA substrates.

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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 [42]

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  • Association of DIS3 and EXOSC10 with the RNA exosome decreases catalytic efficiency through allosteric effects.

    “It has also been suggested that association of DIS3 and EXOSC10 with the RNA exosome decreases catalytic efficiency through allosteric effects42,69.”

    From EXOSC3 G191 Variants Trigger System-Wide Recalibration of RNA Processing Machinery (2026) · cites this paper as [42]

    The Discussion section, “The role of the exosome channel in substrate recruitment” (page unavailable), reports some inhibition of Dis3 activity by the exosome ring. But it also says the channel may increase PIN-domain endonuclease activity through better RNA binding. The paper does not establish that association of both DIS3 and EXOSC10 decreases catalytic efficiency through allosteric effects; it says the authors did not study the Rrp6-containing exosome in vitro. (LLM, conf=0.84)

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Research works printed but not linked: 30

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Cited by

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Authors
Drążkowska, K., Tomecki, R., Stoduś, K., Kowalska, K., Czarnocki-Cieciura, M., & Dziembowski, A.
Affiliations
Institute of Biochemistry and Biophysics, Polish Academy of Sciences (PL)
Corresponding author
Dziembowski, Andrzej
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2013-02-06
Volume
41
Issue
6
Pages
3845-3858
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkt060
PMC
PMC3616716
OpenAlex
W2098474935
Cited by
60
References
2
Citations by year
2026: 3 · 2025: 2 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 6 · 2016: 7 · 2015: 3 · 2014: 7 · 2013: 8
FWCI
3.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
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, DIS3, central channel, endonuclease activity, exonuclease activity, Rrp6, RNA degradation, synthetic lethality, thermosensitivity, Chaetomium thermophilum, RNA processing
MeSH terms
Cell Nucleus, Chaetomium, Cytoplasm, Genes, Lethal, Mutation, Phenotype, Saccharomyces cerevisiae, RNA Stability, Saccharomyces cerevisiae Proteins, Exosome Multienzyme Ribonuclease Complex

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