A NOVEL RECEPTOR-MEDIATED NUCLEAR-PROTEIN IMPORT PATHWAY

Targeting of most nuclear proteins to the cell nucleus is initiated by interaction between the classical nuclear localization signals (NLSs) contained within them and the importin NLS receptor complex. We have recently delineated a novel 38 amino acid transport signal in the hnRN P A1 protein, termed M9, which confers bidirectional transport across the nuclear envelope. We show here that M9-mediated nuclear import occ urs by a novel pathway that is independent of the well-characterized, importin-mediated classical NLS pathway. Additionally, we have identif ied a specific M9-interacting protein, termed transportin, which binds to wild-type M9 but not to transport-defective M9 mutants. Transporti n is a 90 kDa protein, distantly related to importin beta, and we show that it mediates the nuclear import of M9-containing proteins. These findings demonstrate that there are at least two receptor-mediated nuc lear protein import pathways. Furthermore, as hnRNP A1 likely particip ates in mRNA export, it raises the possibility that transportin is a m ediator of this process as well.