A ROLE FOR NUCLEOPORIN FG REPEAT DOMAINS IN EXPORT OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REV PROTEIN AND RNA FROM THE NUCLEUS

The human immunodeficiency virus type 1 Rev protein contains a nuclear export signal (NES) that is required for Rev-mediated RNA export in m ammals as well as in the yeast Saccharomyces cerevisiae. The Rev NES h as been shown to specifically interact with a human (hRIP/RAB1) and a yeast (yRip1p) protein in the two-hybrid assay. Both of these interact ing proteins are related to FG nucleoporins on the basis of the presen ce of typical repeat motifs. This paper shows that Rev is able to inte ract with multiple FG repeat-containing nucleoporins from both S. cere visiae and mammals; moreover, the ability of Rev NES mutants to intera ct with these FG nucleoporins parallels the ability of the mutants to promote RNA export in yeast and mammalian cells. The data also show th at, after Xenopus oocyte nuclear injection, several FG nucleoporin rep eat domains inhibit the export of both Rev protein and U small nuclear RNAs, suggesting that these nucleoporins participate in Rev-mediated and cellular RNA export. Interestingly, not all FG nucleoporin repeat domains produced the same pattern of RNA export inhibition. The result s suggest that Rev and cellular mediators of RNA export can interact w ith multiple components of the nuclear pore complex during transport, analogous to the proposed mode of action of the nuclear protein import receptor.