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Cited by 13interferon and immune responsesGenomics and Chromatin DynamicsDNA Repair Mechanisms

Aicardi–Goutières Syndrome associated mutations of RNase H2B impair its interaction with ZMYM3 and the CoREST histone-modifying complex

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Shapson-Coe, Alexander, Valeiras, Brenda, Wall, Christopher, Rada, Cristina·2019·PLOS ONE
DOI 10.1371/journal.pone.0213553PMC PMC6424451
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Abstract

DNA-RNA hybrids arise in all cell types, and are removed by multiple enzymes, including the trimeric ribonuclease, RNase H2. Mutations in human RNase H2 result in Aicardi-Goutières syndrome (AGS), an inflammatory brain disorder notable for being a Mendelian mimic of congenital viral infection. Previous studies have shown that several AGS-associated mutations of the RNase H2B subunit do not affect trimer stability or catalytic activity and are clustered on the surface of the complex, leading us to speculate that these mutations might impair important interactions of RNase H2 with so far unidentified proteins. In this study, we show that AGS mutations in this cluster impair the interaction of RNase H2 with several members of the CoREST chromatin-silencing complex that include the histone deacetylase HDAC2 and the demethylase KDM1A, the transcriptional regulators RCOR1 and GTFII-I as well as ZMYM3, an MYM-type zinc finger protein. We also show that the interaction is mediated by the zinc finger protein ZMYM3, suggesting that ZMYM3 acts as a novel type of scaffold protein coordinating interactions between deacetylase, demethylase and RNase H type enzymes, raising the question of whether coordination between histone modifications and the degradation of RNA-DNA hybrids may be required to prevent inflammation in humans.

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Authors
Shapson-Coe, A., Valeiras, B., Wall, C., & Rada, C.
Affiliations
MRC Laboratory of Molecular Biology (GB)
Corresponding author
  • Shapson-Coe, Alexander
  • Rada, Cristina
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2019-03-19
Volume
14
Issue
3
Pages
e0213553
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0213553
PMC
PMC6424451
OpenAlex
W2924163571
Cited by
13
References
45
Citations by year
2026: 3 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 2
FWCI
0.20
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
Medical Research Council (MC_U105178806)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
Aicardi-Goutières syndrome, CoREST complex, RNA-DNA hybrids, LSD1, protein-protein interaction, zinc finger proteins, scaffold proteins, histone modifications, neuroinflammation
MeSH terms
Mouse Embryonic Stem Cells, Animals, Histones, Humans, Mutation, Nerve Tissue Proteins, Nervous System Malformations, Nuclear Proteins, Protein Processing, Post-Translational, Ribonuclease H, Autoimmune Diseases of the Nervous System, Multiprotein Complexes, Mice, Histone Deacetylase 2, Histone Demethylases, Co-Repressor Proteins, HEK293 Cells

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