The nuclear import of RNA helicase A is mediated by importin-alpha3.

RNA helicase A (RHA), an ATPase/helicase, regulates the gene expression at various steps including transcriptional activation and RNA processing. RHA is known to shuttle between the nucleus and cytoplasm. We identified the nuclear localization signal (NLS) of RHA and analyzed the nuclear import mechanisms. The NLS of RHA (RHA-NLS) consisting of 19 amino acid residues is highly conserved through species and does not have the consensus classical NLS. In vitro nuclear import assays revealed that the nuclear import of RHA was Ran-dependent and mediated with the classical importin-alpha/beta-dependent pathway. The binding assay indicated that the basic residues in RHA-NLS were used for interaction with importin-alpha. Furthermore, the nuclear import of RHA-NLS was supported by importin-alpha1 and preferentially importin-alpha3. Our results indicate that the nuclear import of RHA is mediated by the importin-alpha3/importin-beta-dependent pathway and suggest that the specificity for importin may regulate the functions of cargo proteins.