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Glucose dissociates DDX21 dimers to regulate mRNA splicing and tissue differentiation
- Source :
- Cell. 186(1)
- Publication Year :
- 2022
-
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.
- Subjects :
- General Biochemistry, Genetics and Molecular Biology
Subjects
Details
- ISSN :
- 10974172
- Volume :
- 186
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....97915faafb36752f79d6715ae2778575