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J. Biol. Chem., Vol. 279, Issue 25, 26563-26570, June 18, 2004
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From the
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universitaät Hamburg, Martinistrasse 52, D-20251 Hamburg and Zentrum für Molekulare Neurobiologie, Abteilung für Elektronenmikroskopie, Universitaäts-Krankenhaus Hamburg-Eppendorf, Martinistrasse 25, 20251 Hamburg, Germany
Here we provide evidence for an interaction-dependent subnuclear trafficking of the human La (hLa) protein, known as transient interaction partner of a variety of RNAs. Among these, precursor transcripts of certain RNAs are located in the nucleoplasm or nucleolus. Here we examined which functional domains of hLa are involved in its nuclear trafficking. By using green fluorescent-hLa fusion proteins, we discovered a nucleolar localization signal and demonstrated its functionality in a heterologous context. In addition, we revealed that the RRM2 motif of hLa is essential both for its RNA binding competence in vitro and in vivo and its exit from the nucleolus. Our data imply that hLa traffics between different subnuclear compartments, which depend decisively on a functional nucleolar localization signal as well as on RNA binding. Directed trafficking of hLa is fully consistent with its function in the maturation of precursor RNAs located in different subnuclear compartments.
Received for publication, January 29, 2004 , and in revised form, March 29, 2004.
* This work was supported by the Deutsche Forschungsgemeinschaft Grant HE 2814/2-3 (to T. H.) and by the Bundesministerium für Bildang und Forschung (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.
To whom correspondence should be addressed: Heinrich-Pette-Institute für Experimentelle Virologie und Immunologie, Universität Hamburg, Postfach 201652, 20251 Hamburg, Germany. Tel.: 49-40-48051-225; Fax: 49-40-48051-222; E-mail: heise{at}hpi.uni-hamburg.de.
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