Implications of RNG140 (caprin2)-mediated translational regulation in eye lens differentiation

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.