DNA editing in DNA/RNA hybrids by adenosine deaminases that act on RNA

Yuxuan Zheng, Claire Lorenzo, Peter A. Beal

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Adenosine deaminases that act on RNA (ADARs) carry out adenosine (A) to inosine (I) editing reactions with a known requirement for duplex RNA. Here, we show that ADARs also react with DNA/RNA hybrid duplexes. Hybrid substrates are deaminated efficiently by ADAR deaminase domains at dA-C mismatches and with E to Q mutations in the base flipping loop of the enzyme. For a long, perfectly matched hybrid, deamination is more efficient with full length ADAR2 than its isolated deaminase domain. Guide RNA strands for directed DNA editing by ADAR were used to target six different 2-deoxyadenosines in the M13 bacteriophage ssDNA genome. DNA editing efficiencies varied depending on the sequence context of the editing site consistent with known sequence preferences for ADARs. These observations suggest the reaction within DNA/RNA hybrids may be a natural function of human ADARs. In addition, this work sets the stage for development of a new class of genome editing tools based on directed deamination of 2-deoxyadenosines in DNA/RNA hybrids.

Original languageEnglish (US)
Pages (from-to)3369-3377
Number of pages9
JournalNucleic Acids Research
Volume45
Issue number6
DOIs
StatePublished - 2016

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Adenosine Deaminase
RNA
DNA
Deamination
Guide RNA
Bacteriophage M13
Inosine
Adenosine
Genome
Mutation

ASJC Scopus subject areas

  • Genetics

Cite this

DNA editing in DNA/RNA hybrids by adenosine deaminases that act on RNA. / Zheng, Yuxuan; Lorenzo, Claire; Beal, Peter A.

In: Nucleic Acids Research, Vol. 45, No. 6, 2016, p. 3369-3377.

Research output: Contribution to journalArticle

Zheng, Yuxuan ; Lorenzo, Claire ; Beal, Peter A. / DNA editing in DNA/RNA hybrids by adenosine deaminases that act on RNA. In: Nucleic Acids Research. 2016 ; Vol. 45, No. 6. pp. 3369-3377.
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