Implications of RNG140 (caprin2)-mediated translational regulation in eye lens differentiation
Implications of RNG140 (caprin2)-mediated translational regulation in eye lens differentiation
复制标题
DOI：
10.1074/jbc.ra120.012715
复制
发表时间：
2020-08
期刊：
影响因子：
--
通讯作者：
K. Nakazawa;Yuichi Shichino;Shintaro Iwasaki;N. Shiina
中科院分区：
文献类型：
--
作者：
K. Nakazawa;Yuichi Shichino;Shintaro Iwasaki;N. Shiina
翻译水平的基因表达调控是决定细胞命运和功能的关键。 RNA 结合蛋白 RNG140 (caprin2) 在眼晶状体分化中发挥作用，据报道在翻译调节中发挥作用。然而，其机制及其在眼睛中的作用仍不清楚。在这里，我们证明 RNG140 与翻译起始因子真核起始因子 3 (eIF3) 结合，并通过涉及抑制 eIF3 依赖性翻译起始的机制来抑制翻译。全面的核糖体分析显示，培养的中国仓鼠卵巢细胞中 RNG140 的过度表达会减少长 mRNA 的翻译，包括与细胞增殖相关的 mRNA 的翻译。 RNG140 介导的翻译调节也在小鼠眼睛中发挥作用，其中 RNG140 敲除增加了长 mRNA 的翻译。参与晶状体分化的 mRNA，例如晶状体蛋白 mRNA，很短，可以逃避 RNG140 的翻译抑制，并在分化晶状体中进行翻译。因此，这项研究提供了对晶状体细胞通过 RNG140 介导的翻译调节从增殖向分化转变的机制基础的见解。
Regulation of gene expression at the translational level is key to determining cell fate and function. An RNA-binding protein, RNG140 (caprin2), plays a role in eye lens differentiation and has been reported to function in translational regulation. However, the mechanism and its role in eyes has remained unclear. Here, we show that RNG140 binds to the translation initiation factor eukaryotic initiation factor 3 (eIF3) and suppresses translation through mechanisms involving suppression of eIF3-dependent translation initiation. Comprehensive ribosome profiling revealed that overexpression of RNG140 in cultured Chinese hamster ovary cells reduces translation of long mRNAs, including those associated with cell proliferation. RNG140-mediated translational regulation also operates in the mouse eye, where RNG140 knockout increased the translation of long mRNAs. mRNAs involved in lens differentiation, such as crystallin mRNAs, are short and can escape translational inhibition by RNG140 and be translated in differentiating lenses. Thus, this study provides insights into the mechanistic basis of lens cell transition from proliferation to differentiation via RNG140-mediated translational regulation.