RNA editing by adenosine deaminases generates RNA and protein diversity

Abstract

RNA editing is defined as a post-transcriptional change of a gene-encoded sequence at the RNA level, excluding alterations due to processes such as pre-mRNA splicing and 3'-end formation. RNA editing is found in many organisms and can occur either by the insertion or deletion of nucleotides or by the substitution of bases by modification. The nucleoside inosine (I) was first detected in cytoplasmic tRNA and was later found in messenger RNA precursors (pre-mRNAs) and in viral transcripts. It is formed by hydrolytic deamination of a genomically encoded adenosine (A) at C6 of the base and this reaction is catalysed by a family of related enzymes. ADARs (for adenosine deaminases acting on RNA) catalyse A to I conversion either promiscuously or site-specifically in pre-mRNAs, viral RNAs and synthetic double-stranded RNAs (dsRNAs), whereas ADATs (for adenosine deaminases acting on tRNA) are involved in inosine formation in tRNAs. ADAT1 generates I at position 37 (3' of the anticodon) in eukaryotic tRNA(Ala). ADAT2 and ADAT3 function as a heterodimer which catalyses inosine formation at the wobble position (position 34) in eukaryotic tRNAs. Here, we review the state of knowledge on ADARs and ADATs and their RNA substrates, with an emphasis on the developments over the past few years that have increased the understanding of the mechanism of action of these enzymes and of the functional consequences of the widespread modification they catalyse.