DDX50 cooperates with STAU1 to effect stabilization of pro-differentiation RNAs

Glucose binding can alter protein oligomerization to enable differentiation. Here, we demonstrate that glucose binding is a general capacity of DExD/H-box RNA helicases, including DDX50, which was found to be essential for the differentiation of diverse cell types. Glucose binding to conserved DDX50...

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Published in:Cell reports (Cambridge) 2025-01, Vol.44 (1), p.115174, Article 115174
Main Authors: Miao, Weili, Porter, Douglas F., Siprashvili, Zurab, Ferguson, Ian D., Ducoli, Luca, Nguyen, Duy T., Ko, Lisa A., Lopez-Pajares, Vanessa, Srinivasan, Suhas, Hong, Audrey W., Yang, Yen-Yu, Cao, Zhongwen, Meyers, Robin M., Meyers, Jordan M., Tao, Shiying, Wang, Yinsheng, Khavari, Paul A.
Format: Article
Language:English
Subjects:
CP: Molecular biology
DDX50
glucose
mRNA stability
RNA helicase
STAU1
tissue differentiation
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Summary:Glucose binding can alter protein oligomerization to enable differentiation. Here, we demonstrate that glucose binding is a general capacity of DExD/H-box RNA helicases, including DDX50, which was found to be essential for the differentiation of diverse cell types. Glucose binding to conserved DDX50 ATP binding sequences altered protein conformation and dissociated DDX50 dimers. DDX50 monomers bound STAU1 to redirect STAU1 from an RNA-decay-promoting complex with UPF1 to a DDX50-STAU1 ribonuclear complex. DDX50 and STAU1 bound and stabilized a common set of essential pro-differentiation RNAs, including JUN, OVOL1, CEBPB, PRDM1, and TINCR, whose structures they also modified. These findings uncover a DDX50-mediated mechanism of reprograming STAU1 from its canonical role in Staufen-mediated mRNA decay to an opposite role stabilizing pro-differentiation RNAs and establish an activity for glucose in controlling RNA structure and stability. [Display omitted] •Glucose binds directly to the ATP-binding site of DDX50 and dissociates DDX50 dimers•DDX50 monomers compete with UPF1 for binding to STAU1•DDX50 and STAU1 modulate the RNA structure of pro-differentiation genes•DDX50 cooperates with STAU1 to stabilize pro-differentiation RNAs In this study, Miao et al. uncover a non-metabolic role of glucose in tissue differentiation. Glucose directly binds to the DDX50 RNA helicase, modulating its function in RNA stability and promoting epidermal differentiation.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2024.115174