Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs

D Weidensdorfer, N Stöhr, A Baude, M Lederer… - Rna, 2009 - rnajournal.cshlp.org
D Weidensdorfer, N Stöhr, A Baude, M Lederer, M Köhn, A Schierhorn, S Buchmeier…
Rna, 2009rnajournal.cshlp.org
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 …
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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