Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs
Abstract
The RNA-binding protein IGF2BP1 (IGF-II mRNA binding protein 1) stabilizes the c-myc RNA by associating with the Coding Region instability Determinant (CRD). If and how other proteins cooperate with IGF2BP1 in promoting stabilization of the c-myc mRNA via the CRD remained elusive. Here, we identify various RNA-binding proteins that associate with IGF2BP1 in an RNA-dependent fashion. Four of these proteins (HNRNPU, SYNCRIP, YBX1, and DHX9) were essential to ensure stabilization of the c-myc mRNA via the CRD. These factors associate with IGF2BP1 in a CRD-dependent manner, co-distribute with IGF2BP1 in non-polysomal fractions comprising c-myc mRNA, and colocalize with IGF2BP1 in the cytoplasm. A selective shift of relative c-myc mRNA levels to the polysomal fraction is observed upon IGF2BP1 knockdown. These findings suggest that IGF2BP1 in complex with at least four proteins promotes CRD-mediated mRNA stabilization. Complex formation at the CRD presumably limits the transfer of c-myc mRNA to the polysomal fraction and subsequent translation-coupled decay.
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Footnotes
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Reprint requests to: Stefan Hüttelmaier, NBL3-NWG6 ZAMED, Department of Medicine, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 1, D-06120 Halle, Germany; e-mail: stefan.huettelmaier{at}medizin.uni-halle.de; fax: +49 345 552 2894.
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.1175909.
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- Received May 9, 2008.
- Accepted October 20, 2008.
- Copyright © 2009 RNA Society