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Aicardi-Goutières Syndrome associated mutations of RNase H2B impair its interaction with ZMYM3 and the CoREST histone-modifying complex.
PLoS One 2019; 14(3):e0213553Plos

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.

Authors+Show Affiliations

MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United Kingdom.MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United Kingdom.MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United Kingdom.MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United Kingdom.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30889214

Citation

Shapson-Coe, Alexander, et al. "Aicardi-Goutières Syndrome Associated Mutations of RNase H2B Impair Its Interaction With ZMYM3 and the CoREST Histone-modifying Complex." PloS One, vol. 14, no. 3, 2019, pp. e0213553.
Shapson-Coe A, Valeiras B, Wall C, et al. Aicardi-Goutières Syndrome associated mutations of RNase H2B impair its interaction with ZMYM3 and the CoREST histone-modifying complex. PLoS ONE. 2019;14(3):e0213553.
Shapson-Coe, A., Valeiras, B., Wall, C., & Rada, C. (2019). Aicardi-Goutières Syndrome associated mutations of RNase H2B impair its interaction with ZMYM3 and the CoREST histone-modifying complex. PloS One, 14(3), pp. e0213553. doi:10.1371/journal.pone.0213553.
Shapson-Coe A, et al. Aicardi-Goutières Syndrome Associated Mutations of RNase H2B Impair Its Interaction With ZMYM3 and the CoREST Histone-modifying Complex. PLoS ONE. 2019;14(3):e0213553. PubMed PMID: 30889214.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aicardi-Goutières Syndrome associated mutations of RNase H2B impair its interaction with ZMYM3 and the CoREST histone-modifying complex. AU - Shapson-Coe,Alexander, AU - Valeiras,Brenda, AU - Wall,Christopher, AU - Rada,Cristina, Y1 - 2019/03/19/ PY - 2018/12/04/received PY - 2019/02/24/accepted PY - 2019/3/20/entrez PY - 2019/3/20/pubmed PY - 2019/3/20/medline SP - e0213553 EP - e0213553 JF - PloS one JO - PLoS ONE VL - 14 IS - 3 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/30889214/Aicardi_Goutières_Syndrome_associated_mutations_of_RNase_H2B_impair_its_interaction_with_ZMYM3_and_the_CoREST_histone_modifying_complex_ L2 - http://dx.plos.org/10.1371/journal.pone.0213553 DB - PRIME DP - Unbound Medicine ER -