Journal of Biological Chemistry
Volume 295, Issue 44, 30 October 2020, Pages 15029-15044
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Cell Biology
Implications of RNG140 (caprin2)-mediated translational regulation in eye lens differentiation

https://doi.org/10.1074/jbc.RA120.012715Get rights and content
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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.

RNA-binding protein
translation
lens
proliferation
differentiation
eukaryotic initiation factor 3
RNG140 (caprin2)

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Author contributions—K. N. and N. S. conceptualization; K. N. investigation; K. N. visualization; K. N. and N. S. writing-original draft; Y. S. and S. I. resources; Y.S. and S. I. methodology; Y. S., S. I., and N. S. writing-review and editing; N. S. supervision; N. S. funding acquisition; N. S. project administration.

Funding and additional information—This work was supported by the Takeda Science Foundation and Grant-in-Aid for Scientific Research 19H03161 from the Japan Society for the Promotion of Science (JSPS) (to N. S.). This work was supported in part by the Graduate University for Advanced Studies, SOKENDAI. S. I. was supported by Grant-in-Aid for Scientific Research on Innovative Areas “nascent chain biology” JP17H05679, Grant-in-Aid for Young Scientists (A) JP17H04998, Challenging Research (Exploratory) Grant JP19K22406 from JSPS, Pioneering Projects (“Cellular Evolution”) and the Aging Project from RIKEN, and the Takeda Science Foundation. Y. S. received JSPS Research Fellowship (PD) 19J00920.

Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article.

Abbreviations—The abbreviations used are:

    RNG

    RNA granule protein

    CHO

    Chinese hamster ovary

    eIF

    eukaryotic initiation factor

    eEF

    eukaryotic elongation factor

    IRES

    internal ribosome entry site

    more-T

    more likely target transcripts

    less-T

    less likely target transcripts

    CDS

    coding sequence

    GO

    gene ontology

    PI3K

    phosphoinositide 3-kinase

    PI4K

    phosphoinositide 4-kinase

    P

    postnatal day

    E

    embryonic day

    qRT-PCR

    quantitative RT-PCR

    WGA

    wheat germ agglutinin

    FBS

    fetal bovine serum

    GST

    glutathione S-transferase

    gRNA

    guide RNA

    mWM

    modified Whitten's medium

    DAPI

    4′,6-diamidino-2-phenylindole

    nt

    nucleotides.