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Mol Cell Biol, March 1998, p. 1449-1458, Vol. 18, No. 3
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Identification and Functional Characterization of a Novel Nuclear Localization Signal Present in the Yeast Nab2 Poly(A)+ RNA Binding Protein

Ray Truant, Robert A. Fridell,dagger R. Edward Benson, Hal Bogerd, and Bryan R. Cullen*

Howard Hughes Medical Institute and Department of Genetics, Duke University Medical Center, Durham, North Carolina 27710

Received 17 September 1997/Returned for modification 30 October 1997/Accepted 19 November 1997

The nuclear import of proteins bearing a basic nuclear localization signal (NLS) is dependent on karyopherin alpha /importin alpha , which acts as the NLS receptor, and karyopherin beta 1/importin beta , which binds karyopherin alpha  and mediates the nuclear import of the resultant ternary complex. Recently, a second nuclear import pathway that allows the rapid reentry into the nucleus of proteins that participate in the nuclear export of mature mRNAs has been identified. In mammalian cells, a single NLS specific for this alternate pathway, the M9 NLS of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), has been described. The M9 NLS binds a transport factor related to karyopherin beta 1, termed karyopherin beta 2 or transportin, and does not require a karyopherin alpha -like adapter protein. A yeast homolog of karyopherin beta 2, termed Kap104p, has also been described and proposed to play a role in the nuclear import of a yeast hnRNP-like protein termed Nab2p. Here, we define a Nab2p sequence that binds to Kap104p and that functions as an NLS in both human and yeast cells despite lacking any evident similarity to basic or M9 NLSs. Using an in vitro nuclear import assay, we demonstrate that Kap104p can direct the import into isolated human cell nuclei of a substrate containing a wild-type, but not a defective mutant, Nab2p NLS. In contrast, other NLSs, including the M9 NLS, could not function as substrates for Kap104p. Surprisingly, this in vitro assay also revealed that human karyopherin beta 1, but not the Kap104p homolog karyopherin beta 2, could direct the efficient nuclear import of a Nab2p NLS substrate in vitro in the absence of karyopherin alpha . These data therefore identify a novel NLS sequence, active in both yeast and mammalian cells, that is functionally distinct from both basic and M9 NLS sequences.

* Corresponding author. Mailing address: Box 3025, Room 426 CARL Building, Research Dr., Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-3369. Fax: (919) 681-8979. E-mail: Culle002{at}mc.duke.edu.

dagger Present address: Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, Rockville, MD 20850.




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