The human but not the Xenopus RNA-editing enzyme ADAR1 has an atypical nuclear localization signal and displays the characteristics of a shuttling protein

The RNA-editing enzyme ADAR1 (adenosine deaminase that acts on RNA) is a bo na fide nuclear enzyme that has been cloned from several vertebrate species . Putative nuclear localization signals (NLSs) have been identified in the aminoterminal regions of both human and Xenopus ADAR1 Here we show that nei ther of these predicted NLSs is biologically active. Instead, we could iden tify a short basic region located upstream of the RNA-binding domains of Xe nopus ADAR1 to be necessary and sufficient for nuclear import. In contrast, the homologous region in human ADAR1 does not display NLS activity. Instea d, we could map an NLS in human ADAR1 that overlaps with its third double-s tranded RNA-binding domain. Interestingly, the NLS activity displayed by th is double-stranded RNA-binding domain does not depend on RNA binding, there fore showing a dual function for this domain. Furthermore, nuclear accumula tion of human (hs) ADAR1 is transcription dependent and can be stimulated b y LMB, an inhibitor of Crm1-dependent nuclear export, indicating that hsADA R1 can move between the nucleus and cytoplasm. Regulated nuclear import and export of hsADAR1 can provide an excellent mechanism to control nuclear co ncentration of this editing enzyme thereby preventing hyper-editing of stru ctured nuclear RNAs.