Yb. Kang et Br. Cullen, The human Tap protein is a nuclear mRNA export factor that contains novel RNA-binding and nucleocytoplasmic transport sequences, GENE DEV, 13(9), 1999, pp. 1126-1139
The constitutive transport element (CTE) encoded by simian type D retroviru
ses directs unspliced viral RNAs into a nuclear export pathway that is cong
ruent with the pathway used by cellular mRNAs. Here, we show that quail cel
ls are refractory to CTE function but become highly permissive upon express
ion of the human Tap protein, a candidate CTE cofactor. Tap contains a nove
l sequence-specific RNA binding domain that is sufficient for CTE binding b
ut inadequate to support CTE function. Using microinjection assays, we have
defined two NLSs and one NES in Tap. Mutational inactivation of the Tap NE
S, which lies outside the RNA-binding domain, not only blocks Tap function
but also generates dominant-negative forms of Tap. Whereas replacement of t
he Tap NES with the well-defined Rev NES rescues the ability of Tap to supp
ort CTE function, this substitution also confers sensitivity to agents that
block the activity of Crm1, the Rev NES cofactor. Together, these data val
idate Tap as the first human sequence-specific nuclear mRNA export factor a
nd identify a novel type of NES that can support nuclear mRNA export but do
es not act via Crm1.