DNA editing in DNA/RNA hybrids by adenosine deaminases that act on RNA.
Nucleic Acids Res
; 45(6): 3369-3377, 2017 04 07.
Article
en En
| MEDLINE
| ID: mdl-28132026
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 2Î-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 2Î-deoxyadenosines in DNA/RNA hybrids.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
ADN
/
ARN
/
Adenosina Desaminasa
/
Proteínas de Unión al ARN
Límite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos