NUCLEAR IMPORT AND THE EVOLUTION OF A MULTIFUNCTIONAL RNA-BINDING PROTEIN

La (SS-B) is a highly expressed protein that is able to bind 3'-oligou ridylate and other common RNA sequence/structural motifs. By virtue of these interactions, La is present in a myriad of nuclear and cytoplas mic ribonucleoprotein complexes in vivo where it may function as an RN A-folding protein or RNA chaperone. We have recently characterized the nuclear import pathway of the S. cerevisiae La, Lhp1p. The soluble tr ansport factor, or karyopherin, that mediates the import of Lhp1p is K ap108p/Sxm1p. We have now determined a 113-amino acid domain of Lhp1p that is brought to the nucleus by Kap108p. Unexpectedly, this domain d oes not coincide with the previously identified nuclear localization s ignal of human La. Furthermore, when expressed in Saccharomyces cerevi siae, the nuclear localization of Schizosaccharomyces pombe, Drosophil a, and human La proteins are independent of Kap108p. We have been able to reconstitute the nuclear import of human La into permeabilized HeL a cells using the recombinant human factors karyopherin alpha 2, karyo pherin beta 1, Ran, and p10. As such, the yeast and human La proteins are imported using different sequence motifs and dissimilar karyopheri ns. Our results are consistent with an intermingling of the nuclear im port and evolution of La.