美国斯坦福大学Paul A. Khavari小组发现，葡萄糖解聚DDX21二聚体来调节mRNA剪接和组织分化。2023年1月5日出版的《细胞》杂志发表了这项成果。

Title: Glucose dissociates DDX21 dimers to regulate mRNA splicing and tissue differentiation

Author: Weili Miao, Douglas F. Porter, Vanessa Lopez-Pajares, Zurab Siprashvili, Robin M. Meyers, Yunhao Bai, Duy T. Nguyen, Lisa A. Ko, Brian J. Zarnegar, Ian D. Ferguson, Matthew M. Mills, Christie E. Jilly-Rehak, Cheng-Guo Wu, Yen-Yu Yang, Jordan M. Meyers, Audrey W. Hong, David L. Reynolds, Muthukumar Ramanathan, Shiying Tao, Sizun Jiang, Ryan A. Flynn, Yinsheng Wang, Garry P. Nolan, Paul A. Khavari

Issue&Volume: 2023/01/05

Abstract: 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.

DOI: 10.1016/j.cell.2022.12.004

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01517-3