Key result
The presence of a Z-RNA forming nucleotide sequence markedly enhanced A-to-I editing efficiency by ADAR1 in vitro.
The local conformation of dsRNA molecules, specifically the presence of Z-RNA, enhances ADAR1 editing efficiency in vitro, suggesting its importance for target selectivity.
In vitro Z-RNA data warrant cellular and in vivo validation; leaves open any role in disease or therapeutic RNA editing.
RNA editing by A-to-I modification has been recognized as an important molecular mechanism for generating RNA and protein diversity. In mammals, it is mediated by a family of adenosine deaminases that act on RNAs (ADARs). The large version of the editing enzyme ADAR1 (ADAR1-L), expressed from an interferon-responsible promoter, has a Z-DNA/Z-RNA binding domain at its N-terminus. We have tested the in vitro ability of the enzyme to act on a 50 bp segment of dsRNA with or without a Z-RNA forming nucleotide sequence. A-to-I editing efficiency is markedly enhanced in presence of the sequence favoring Z-RNA. In addition, an alteration in the pattern of modification along the RNA duplex becomes evident as reaction times decrease. These results suggest that the local conformation of dsRNA molecules might be an important feature for target selectivity by ADAR1 and other proteins with Z-RNA binding domains.
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Michael Koeris (2005) studied this question. Presence of Z-RNA forming nucleotide sequence vs. Absence of Z-RNA forming nucleotide sequence was evaluated on A-to-I editing efficiency. The presence of a Z-RNA forming nucleotide sequence markedly enhanced A-to-I editing efficiency by ADAR1 in vitro.
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