Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs
Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs
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DOI：
10.1261/rna.1175909
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发表时间：
2009-01-01
期刊：
影响因子：
4.5
通讯作者：
Huettelmaier, Stefan
中科院分区：
文献类型：
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作者：
Weidensdorfer, Doreen;Stoehr, Nadine;Huettelmaier, Stefan
RNA结合蛋白IGF 2BP 1（IGF-II mRNA结合蛋白1）通过与编码区不稳定性决定簇（CRD）结合来稳定c-myc RNA。其他蛋白质是否以及如何与IGF 2BP 1合作通过CRD促进c-myc mRNA的稳定仍然是难以捉摸的。在这里，我们确定了各种RNA结合蛋白，与IGF 2BP 1在RNA依赖的方式。这些蛋白质中的四种（HNRNPU、SYNCRIP、YBX 1和DHX 9）对于通过CRD确保c-myc mRNA的稳定是必不可少的。这些因子以CRD依赖性方式与IGF 2BP 1相关，与IGF 2BP 1共分布在包含c-myc mRNA的非多聚体组分中，并与IGF 2BP 1共定位在细胞质中。IGF 2BP 1敲低后，观察到相对c-myc mRNA水平向多核糖体部分的选择性转移。这些发现表明，IGF 2BP 1与至少四种蛋白质复合促进CRD介导的mRNA稳定。在CRD复合物的形成大概限制了c-myc mRNA转移到多聚体组分和随后的抑制偶联衰变。
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.