Transportin2 functions as importin and mediates nuclear import of HuR

doi:10.1073/pnas.0400342101

Transportin2 functions as importin and mediates nuclear import of HuR

^*Swiss Federal Institute of Technology, Institute of Biochemistry, HPM F11.1, 8093 Zürich, Switzerland; and ^†European Molecular Biology Laboratory, 69117 Heidelberg, Germany

Communicated by James E. Dahlberg, University of Wisconsin Medical School, Madison, WI, January 15, 2004 (received for review November 10, 2003)

Abstract

The RanGTP-binding nuclear transport receptors transportin1 (TRN1) and transportin2 (TRN2) are highly similar in sequence but are reported to function in nuclear import and export, respectively. Here we show that TRN2 possesses properties of a nuclear import receptor. TRN1/2 both interacted with a similar set of RNA-binding proteins in a RanGTP-sensitive manner. TRN2 bound RanGTP with high affinity, a feature of nuclear import receptors. As expected of an import complex, RanGTP also disrupted the interaction between TRN2 and HuR, an RNA-binding protein previously described as a TRN2 export substrate. The HuR nucleocytoplasmic shuttling signal, a sequence resembling the M9 nuclear import signal of hnRNP A1, was necessary and sufficient for TRN-mediated nuclear import of HuR in vitro. Finally, crosscompetition experiments demonstrated that HuR nucleocytoplasmic shuttling signal and M9 are imported along redundant pathways involving TRN1/2, substantiating the function of TRN2 in nuclear import.

Footnotes

↵ ‡ To whom correspondence should be addressed. E-mail: ulrike.kutay{at}bc.biol.ethz.ch.
Abbreviations: TRN, transportin; HNS, HuR nucleocytoplasmic shuttling signal; NPC, nuclear pore complex; ARE, AU-rich element; hnRNP, heterogeneous nuclear ribonucleoprotein; VEGF, vascular endothelial growth factor.