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J. Biol. Chem., Vol. 279, Issue 42, 43437-43447, October 15, 2004

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Functional Characterization of the Interaction between Human La and Hepatitis B Virus RNA^*

Imke Ehlers, Sven Horke, Kerstin Reumann, Andreas Rang¶, Frank Grosse||, Hans Will, and Tilman Heise**

From the Heinrich-Pette Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Martinistrasse 52, D-20251 Hamburg and ^||Institut für Molekulare Biotechnologie, Abteilung Biochemie, Beutenbergstrasse 11, D-07745 Jena, Germany

The La protein is a multifunctional RNA-binding protein and has also been suggested to be involved in the stabilization of hepatitis B virus (HBV) RNA. Here we demonstrate that antibodies against the human La protein specifically precipitate HBV RNA from HBV ribonucleoprotein-containing mammalian cell extracts, providing evidence for the association between human La and HBV RNA. Moreover, we report that the turnover of HBV RNA depends on structural features and less on the primary sequence of the La-binding site on the viral RNA. In addition we show that the interaction between human La and HBV RNA in vitro is modulated by accessory factor(s) in a phosphorylation-dependent manner. Taken together these data indicate that both structural features, the composition of La/HBV ribonucleoprotein particles as well as interacting cellular factors, are critical determinants in the regulation of the stability of the HBV RNA.

Received for publication, February 27, 2004 , and in revised form, August 6, 2004.

^* This work was supported by Deutsche Forschungsgemeinschaft Grants HE 2814/2-3 (to T. H.), WI 664/9-1 (to H. W.), and the Bundesministerium für Bildung und Forshchung (Nationales Genomforschungsnetz and Kompetenznetz Hepatitis). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10021.

^¶ Present address: Institute of Virology, University Hospital Charité, Schumannstr. 20/21, D-10098 Berlin, Germany.

^** To whom correspondence should be addressed: Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Universität Hamburg, Postfach 201652, 20206 Hamburg, Germany. Tel.: 49-40-48051-225; Fax: 49-40-48051-222; E-mail: heise{at}hpi.uni-hamburg.de.

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