The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast tohuman

Human TAP is an orthologue of the yeast mRNA export factor Mex67p. In mamma lian cells, TAP has a preferential intranuclear localization, but can also be detected at the nuclear pores and shuttles between the nucleus and the c ytoplasm, TAP directly associates with mRNA in vivo, as it can be UV-crossl inked to poly(A)(+) RNA in HeLa cells. Both the FG-repeat domain of nucleop orin CAN/Nup214 and a novel human 15 kDa protein (p15) with homology to NTF 2 (a nuclear transport factor which associates with RanGDP), directly bind to TAP. When green fluorescent protein (GFP)-tagged TAP and p15 are express ed in yeast, they localize to the nuclear pores. Strikingly, co-expression of human TAP and p15 restores growth of the otherwise lethal mex67::HIS3/mt r2::HIS3 double knockout strain, Thus, the human TAP-p15 complex can functi onally replace the Mex67p-Mtr2p complex in yeast and thus performs a conser ved role in nuclear mRNA export.