ArticleThe Journal of biological chemistry2011
Functional consequences of the RNase H2A subunit mutations that cause Aicardi-Goutieres syndrome.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Ultrasensitive RNase H activity detection using the transcription-based hybrid probe and CRISPR/cas12a signal amplifier.Frontiers in pharmacology · 2025Article
- Second generation lethality in RNAseH2a knockout zebrafish.Nucleic acids research · 2024Article
- Distinct features of ribonucleotides within genomic DNA in Aicardi-Goutières syndrome ortholog mutants ofiScience · 2024Article
- Mechanistic investigation of human maturation of Okazaki fragments reveals slow kinetics.Nature communications · 2022Article
- Val143 of human ribonuclease H2 is not critical for, but plays a role in determining catalytic activity and substrate specificity.PloS one · 2020Article
- Characterization of six recombinant human RNase H2 bearing Aicardi-Goutiéres syndrome causing mutations.Journal of biochemistry · 2019Article
- RNase H2-RED carpets the path to eukaryotic RNase H2 functions.DNA repair · 2019Review
- Article
- The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders.International review of cell and molecular biology · 2019Review
- Rotational and translational positions determine the structural and dynamic impact of a single ribonucleotide incorporated in the nucleosome.DNA repair · 2019Article
- Two RNase H2 Mutants with Differential rNMP Processing Activity Reveal a Threshold of Ribonucleotide Tolerance for Embryonic Development.Cell reports · 2018Article
- LINE-1 retrotransposons in healthy and diseased human brain.Developmental neurobiology · 2018Review
- Effects of neutral salts and pH on the activity and stability of human RNase H2.Journal of biochemistry · 2017Article
- Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates.Genome biology and evolution · 2017Article
- RNase H2 catalytic core Aicardi-Goutières syndrome-related mutant invokes cGAS-STING innate immune-sensing pathway in mice.The Journal of experimental medicine · 2016Article
- Reduction of hRNase H2 activity in Aicardi-Goutières syndrome cells leads to replication stress and genome instability.Human molecular genetics · 2015Article
- Synonymous mutations in RNASEH2A create cryptic splice sites impairing RNase H2 enzyme function in Aicardi-Goutières syndrome.Human mutation · 2013Article
- RNase H2 roles in genome integrity revealed by unlinking its activities.Nucleic acids research · 2013Article
- Human DNA polymerase ε is able to efficiently extend from multiple consecutive ribonucleotides.The Journal of biological chemistry · 2012Article
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the three genes encoding the heterotrimeric RNase H2 complex cause Aicardi-Goutières Syndrome (AGS). Our mouse RNase H2 structure revealed that the catalytic RNase H2A subunit interfaces mostly with the RNase H2C subunit that is intricately interwoven with the RNase H2B subunit. We mapped the positions of AGS-causing RNase H2A mutations using the mouse RNase H2 structure and proposed that these mutations cause varied effects on catalytic potential. To determine the functional consequences of these mutations, heterotrimeric human RNase H2 complexes containing the RNase H2A subunit mutations were prepared, and catalytic efficiencies and nucleic acid binding properties were compared with the wild-type (WT) complex. These analyses reveal a dramatic range of effects with mutations at conserved positions G37S, R186W, and R235Q, reducing enzymatic activities and substrate binding affinities by as much as a 1000-fold, whereas mutations at non-conserved positions R108W, N212I, F230L, T240M, and R291H reduced activities and binding modestly or not at all. All mutants purify as three-subunit complexes, further supporting the required heterotrimeric structure in eukaryotic RNase H2. These kinetic properties reveal varied functional consequences of AGS-causing mutations in the catalytic RNase H2A subunit and reflect the complex mechanisms of nuclease dysfunction that include catalytic deficiencies and altered protein-nucleic acid interactions relevant in AGS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.