HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 11, 7046-7053, March 14, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/11/7046    most recent M709613200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Holmström, T. H. Articles by Westermarck, J. PubMed PubMed Citation Articles by Holmström, T. H. Articles by Westermarck, J. Social Bookmarking                      What's this?

c-Jun Supports Ribosomal RNA Processing and Nucleolar Localization of RNA Helicase DDX21^*

Tim H. Holmström¹, Antoine Mialon, Marko Kallio, Yvonne Nymalm^¶, Leni Mannermaa, Tina Holm^||, Henrik Johansson^||, Elizabeth Black^**, David Gillespie^**, Tiina A. Salminen^¶, Ülo Langel^||, Benigno C. Valdez, and Jukka Westermarck^¶¶2

From the Centre for Biotechnology, University of Turku and Åbo Akademi University, 20520 Turku, Finland, the ^¶¶Institute of Medical Technology, University of Tampere and the Tampere University Hospital, 33520 Tampere, Finland, the State Technical Research Center of Finland, Medical Biotechnology, 20521 Turku, Finland, the ^¶Department of Biochemistry and Pharmacy, Åbo Akademi University, 20520 Turku, Finland, the ^||Department of Neurochemistry, University of Stockholm, 10691 Stockholm, Sweden, the ^**Beatson Institute for Cancer Research, Glasgow G61 1BD, Scotland, United Kingdom, the Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, United Kingdom, and the Department of Blood and Marrow Transplantation, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030

The molecular mechanisms by which the AP-1 transcription factor c-Jun exerts its biological functions are not clearly understood. In addition to its well established role in transcriptional regulation of gene expression, several reports have suggested that c-Jun may also regulate cell behavior by non-transcriptional mechanisms. Here, we report that small interfering RNA-mediated depletion of c-Jun from mammalian cells results in inhibition of 28 S and 18 S rRNA accumulation. Moreover, we show that c-Jun depletion results in partial translocation of RNA helicase DDX21, implicated in rRNA processing, from the nucleolus to the nucleoplasm. We demonstrate that DDX21 translocation is rescued by exogenous c-Jun expression and that c-Jun depletion inhibits rRNA binding of DDX21. Furthermore, the direct interaction between c-Jun and DDX21 regulates nucleolar localization of DDX21. These results demonstrate that in addition to its transcriptional effects, c-Jun regulates rRNA processing and nucleolar compartmentalization of the rRNA processing protein DDX21. Thus, our results demonstrate a nucleolar mechanism through which c-Jun can regulate cell behavior. Moreover, these results suggest that the phenotypes observed previously in c-Jun-depleted mouse models and cell lines could be partly due to the effects of c-Jun on rRNA processing.

Received for publication, November 26, 2007 , and in revised form, January 4, 2008.

^* This work was supported in part by the Academy of Finland (Projects 878179 and 8212695), the Sigrid Juselius Foundation, and the Finnish Cancer Association. 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S5.

¹ Supported by a Human Frontier Science Program Organization long-term fellowship, Stiftelsen för Åbo Akademis Forskningsinstitut, and the Foundation for the Finnish Cancer Institute.

² To whom correspondence should be addressed: Inst. of Medical Technology, University of Tampere, 33520 Tampere, Finland. E-mail: ltjuwe{at}uta.fi.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?