NUCLEAR IMPORT OF HNRNP A1 IS MEDIATED BY A NOVEL CELLULAR COFACTOR RELATED TO KARYOPHERIN-BETA

Heterogeneous nuclear ribonucleoprotein Al contains a sequence, termed M9, that functions as a potent nuclear localization signal (NLS) yet bears no similarity to the well-defined basic class of NLSs. Here, we report the identification of a novel human protein, termed MIP, that b inds M9 specifically both in vivo and in vitro yet fails to interact w ith non-functional M9 point mutants, Of note, the 101 kDa MIP protein bears significant homology to human karyopherin/importin-beta, a prote in known to mediate the function of basic NLSs. The in vitro nuclear i mport of a protein substrate containing the M9 NLS was found to be dep endent on provision of the MIP protein in trans, Cytoplasmic microinje ction of a truncated form of MIP that retains the M9 binding site bloc ked the in vivo nuclear import of a substrate containing the M9 NLS ye t failed to affect the import of a similar substrate bearing a basic N LS, These data indicate that nuclear import of hnRNP Al is mediated by a novel cellular import pathway that is distinct from, Set evolutiona rily related to, the pathway utilized by basic NLS sequences.