Glucose dissociates DDX21 dimers to regulate mRNA splicing and tissue differentiation.
Cell
; 186(1): 80-97.e26, 2023 01 05.
Article
en En
| MEDLINE
| ID: mdl-36608661
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Queratinocitos
/
ARN Helicasas DEAD-box
/
Glucosa
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article