Nucleus/cytosol exchange in eukaryotes requires a
GTPase, Ran. In yeast RNA1 encodes Rna1p, the G TPase
a ctivating p rotein for Ran (RanGAP), and the Ran
G DP/GTP e xchange f actor (GEF) is encoded by
PRP20 . In all organisms, RanGAP is located primarily in the
cytosol, and the GEF is located in the nucleus. The subcellular
distributions led to the prediction that Ran-GTP hydrolysis takes place
solely in the cytosol and GDP/GTP exchange solely in the nucleus. We
provide two lines of evidence that Rna1p is a nucleus/cytosol shuttling
protein: (1) Rna1p possesses sequences similar to n uclear
e xport s equences (NES), necessary for nucleus/cytosol
exchange of some shuttling proteins; (2) we expressed Rna1p in a
crm1/xpo1 yeast strain defective in shuttling of NES-containing
proteins and found that Rna1p rapidly accumulates in the nucleus in this
strain at the nonpermissive temperature. The data support the notion
that Rna1p could function on both sides of the nuclear membrane and
raise alternative models: (1) there may be a complete Ran cycle on both
sides of the yeast membrane and GTP to GDP hydrolysis could play a role
in the import and export processes; (2) nuclear Rna1p could be a
regulator of nucleus/cytosol exchange by affecting the gradient of
nuclear RanGTP versus cytosolic RanGDP; (3) nuclear pools of Rna1p may
participate in a process(es) distinct from exchange.
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