THE K-NUCLEAR-SHUTTLING-DOMAIN - A NOVEL SIGNAL FOR NUCLEAR IMPORT AND NUCLEAR EXPORT IN THE HNRNP-K-PROTEIN

Protein import into the nucleus and export from the nucleus are signal -mediated processes that require energy. The nuclear transport process about which the most information is currently available is classical nuclear localization signal (NLS)-mediatedl nuclear import. However, d etails concerning the signal-mediated export of proteins and RNAs as w ell as alternative nuclear import pathways are beginning to emerge. An example of this is the heterogeneous nuclear ribonucleoprotein (hnRNP ) Al protein which, by virtue of its M9 domain, is actively exported f rom the nucleus and imported into the nucleus via a novel pathway medi ated by the recently characterized transportin protein. Here we report that the shuttling hnRNP K protein contains a novel shuttling domain (termed KNS) which has many of the characteristics of M9, in that it c onfers bi-directional transport across the nuclear envelope. KNS-media ted nuclear import is dependent on RNA polymerase II transcription, an d we show that a classical NLS can override this effect. Furthermore, KNS accesses a separate import pathway from either classical NLSs or M 9. This demonstrates the existence of a third protein import pathway i nto the nucleus and thereby defines a new type of nuclear import/expor t signal.