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Article
Subject Categories: Proteins | Cell Cycle
The EMBO Journal (2007) 26, 158–169, doi:10.1038/sj.emboj.7601468
Published online 7 December 2006
A role for hnRNP C1/C2 and Unr in internal initiation of translation during mitosis
Bert Schepens1, Sandrine A Tinton1, Yanik Bruynooghe1, Eef Parthoens2, Mira Haegman1, Rudi Beyaert1, 3 and Sigrid Cornelis1, 3
1 Unit of Molecular Signal Transduction in Inflammation, Department for Molecular Biomedical Research, VIB-Ghent University, Gent-Zwijnaarde, Belgium
2 Microscopy Core Facility, Department for Molecular Biomedical Research, VIB-Ghent University, Gent-Zwijnaarde, Belgium
3 These authors contributed equally to this work

To whom correspondence should be addressed

Rudi Beyaert, Department for Molecular Biomedical Research, VIB-Ghent University, Technologiepark 927, 9052 Gent (Zwijnaarde), Belgium. Tel.: +32 9 3313 600; Fax: +32 9 3313 609; E-mail: Rudi.Beyaert@dmbr.ugent.be
Sigrid Cornelis, Tel.: +32 9 3313 770; Fax: +32 9 3313 609; E-mail: Sigrid.Cornelis@dmbr.ugent.be

Received 17 May 2006; Accepted 6 November 2006; Published online 7 December 2006.
Abstract
The upstream of N-Ras (Unr) protein is involved in translational regulation of specific genes. For example, the Unr protein contributes to translation mediated by several viral and cellular internal ribosome entry sites (IRESs), including the PITSLRE IRES, which is activated at mitosis. Previously, we have shown that translation of the Unr mRNA itself can be initiated through an IRES. Here, we show that UNR mRNA translation and UNR IRES activity are significantly increased during mitosis. Functional analysis identified hnRNP C1/C2 proteins as UNR IRES stimulatory factors, whereas both polypyrimidine tract-binding protein (PTB) and Unr were found to function as inhibitors of UNR IRES-mediated translation. The increased UNR IRES activity during mitosis results from enhanced binding of the stimulatory hnRNP C1/C2 proteins and concomitant dissociation of PTB and Unr from the UNR IRES RNA. Our data suggest the existence of an IRES-dependent cascade in mitosis comprising hnRNP C1/C2 proteins that stimulate Unr expression, and Unr, in turn, contributes to PITSLRE IRES activity. The observation that RNA interference-mediated knockdown of hnRNP C1/C2 and Unr, respectively, abrogates and retards mitosis points out that regulation of IRES-mediated translation by hnRNP C1/C2 and Unr might be important in mitosis.
Keywords: hnRNP C1/C2, IRES, mitosis, translation, Unr
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