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J. Biol. Chem. 276 (50): 47277-47284

© 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

The UV-inducible RNA-binding Protein A18 (A18 hnRNP) Plays a Protective Role in the Genotoxic Stress Response*

Chonglin Yang and France CarrierDagger

From the Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201-1503

We have previously shown that specific RNA-binding proteins (RBP) are activated by genotoxic stress. The role and function of these stress-activated RBP are, however, poorly understood. The data presented here indicate that the RBP A18 heterogeneous ribonucleoprotein (hnRNP) is induced and translocated from the nuclei to the cytoplasm after exposure to UV radiation. Using a new in vitro system we identified potential cellular targets for A18 hnRNP. Forty-six mRNA transcripts were identified, most of which are stress- or UV-responsive genes. Two important stress-responsive transcripts, the replication protein A (RPA2) and thioredoxin, were studied in more detail. Northwestern analyses indicate that A18 hnRNP binds specifically to the 3'-untranslated region of RPA2 transcript independently of its poly(A) tail, whereas the poly(A) tail of thioredoxin mRNA reinforces binding. Overexpression of A18 hnRNP increases the mRNAs stability and consequently enhances translation in a dose-dependent manner. Moreover, cell lines expressing reduced levels of A18 hnRNP are more sensitive to UV radiation. These data suggest that A18 hnRNP plays a protective role against genotoxic stresses by translocating to the cytosol and stabilizing specific transcripts involved in cell survival.

* This work was supported by NIGMS, National Institutes of Health Grant RO1GM57827-01. (to F. C.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: 108 N. Greene St., Rm. 330, Baltimore, MD 21201-1503. Tel.: 410-706-5105; Fax: 410-706-8297; E-mail: fcarr001@umaryland.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

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