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  • Glucose dissociates DDX21 dimers to regulate mRNA splicing and tissue differentiation. Cell Miao, W., Porter, D. F., Lopez-Pajares, V., Siprashvili, Z., Meyers, R. M., Bai, Y., Nguyen, D. T., Ko, L. A., Zarnegar, B. J., Ferguson, I. D., Mills, M. M., Jilly-Rehak, C. E., Wu, C., Yang, Y., Meyers, J. M., Hong, A. W., Reynolds, D. L., Ramanathan, M., Tao, S., Jiang, S., Flynn, R. A., Wang, Y., Nolan, G. P., Khavari, P. A. 2023; 186 (1): 80


    Glucose is a universal bioenergy source; however, its role in controlling protein interactions is unappreciated, as are its actions during differentiation-associated intracellular glucose elevation. Azido-glucose click chemistry identified glucose binding to a variety of RNA binding proteins (RBPs), including the DDX21 RNA helicase, which was found to be essential for epidermal differentiation. Glucose bound the ATP-binding domain of DDX21, altering protein conformation, inhibiting helicase activity, and dissociating DDX21 dimers. Glucose elevation during differentiation was associated with DDX21 re-localization from the nucleolus to the nucleoplasm where DDX21 assembled into larger protein complexes containing RNA splicing factors. DDX21 localized to specific SCUGSDGC motif in mRNA introns in a glucose-dependent manner and promoted the splicing of key pro-differentiation genes, including GRHL3, KLF4, OVOL1, and RBPJ. These findings uncover a biochemical mechanism of action for glucose in modulating the dimerization and function of an RNA helicase essential for tissue differentiation.

    View details for DOI 10.1016/j.cell.2022.12.004

    View details for PubMedID 36608661