Dbp5, a DEAD-box protein required for mRNA export, is recruited to the cytoplasmic fibrils of nuclear pore complex via a conserved interaction with CAN/Nup159p

Dbp5 is a DEAD-box protein essential for mRNA export from the nucleus in ye ast. Here we report the isolation of a cDNA encoding human Dbp5 (hDbp5) whi ch is 46% identical to SDbp5p. Like its yeast homologue, hDbp5 is localized within the cytoplasm and at the nuclear rim. BS immunoelectron microscopy, the nuclear envelope-bound fraction of Dbp5 has been localized to the cyto plasmic fibrils of the nuclear pore complex (NPC). Consistent with this loc alization, we show that both the human and yeast proteins directly interact with an N-terminal region of the nucleoporins CAN/Nup159p, In a conditiona l yeast strain in which Nup159p is degraded when shifted to the nonpermissi ve temperature, yDbp5p dissociates from the NPC and localizes to the cytopl asm, Thus, Dbp5 is recruited to the NPC via a conserved interaction with CA N/Nup159p. To investigate its function, we generated defective hDbp5 mutant s and analysed their effects in RNA export by microinjection in Xenopus ooc ytes, A mutant protein containing a Glu-->Gln change in the conserved DEAD- box inhibited the nuclear exit of mRNAs, Together, our data indicate that D bp5 is a conserved RNA-dependent ATPase which is recruited to the cytoplasm ic fibrils of the NPC where it participates in the export of mRNAs out of t he nucleus.