The carboxyl terminus of RNA helicase A contains a bidirectional nuclear transport domain

Human RNA helicase A was recently identified to be a shuttle protein which interacts with the constitutive transport element (CTE) of type D retroviru ses. Here we show that a domain of 110 amino acids at the carboxyl terminus of helicase A is both necessary and sufficient for nuclear localization as well as rapid nuclear export of glutathione S-transferase fusion proteins. The import and export activities of this domain overlap but are separable by point mutations. This bidirectional nuclear transport domain (NTD) has n o obvious sequence homology to previously identified nuclear import or expo rt signals. However, the Ran-dependent nuclear import of NTD was efficientl y competed by excess amounts of the nuclear localization signal (NLS) pepti de from simian virus 40 large T antigen, suggesting that import is mediated by the classical NLS pathway. The nuclear export pathway accessed by NTD i s insensitive to leptomycin B and thus is distinct from the leucine-rich nu clear export signal pathway mediated by CRM1.