A prominent modification of neuronal transcripts is the deamination of adenosine to inosine (A-to-I) in double-stranded RNA, resulting in alterations in protein sequences or splicing patterns. The extent of RNA editing increases throughout development from the embryonic to the adult brain and is catalysed by one of the two active adenosine deaminases that act on RNA (ADAR1 and ADAR2). Because the mechanisms for A-to-I editing in neuronal development are largely unknown, on page 745 in this issue, Marie Öhmann and colleagues investigate the cellular behaviour of ADAR2 in neurons. They show that A-to-I RNA editing increases during the maturation of cultured neurons with a concomitant increase in nuclear accumulation of ADAR2. The nuclear localisation of ADAR2 depends on two nuclear localisation signals within its N-terminus and on interaction with the adaptor protein importin-α4. The authors report that levels of importin-α4 increase during neuronal cell development and positively regulate ADAR2-specific RNA editing by translocating ADAR2 into the nucleus. They further show that ADAR2 is stabilised within the nucleus by interaction with the peptidyl-prolyl isomerase Pin1 and that this interaction increases during neuronal maturation. In summary, these findings provide a cellular pathway for enhanced RNA editing during development that is regulated by increased nuclear import of the ADAR2 enzyme.
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