DDX50 cooperates with STAU1 to effect stabilization of pro-differentiation RNAs
Weili Miao,
Douglas F. Porter,
Zurab Siprashvili,
Ian D. Ferguson,
Luca Ducoli,
Duy T. Nguyen,
Lisa A. Ko,
Vanessa Lopez-Pajares,
Suhas Srinivasan,
Audrey W. Hong,
Yen-Yu Yang,
Zhongwen Cao,
Robin M. Meyers,
Jordan M. Meyers,
Shiying Tao,
Yinsheng Wang,
Paul A. Khavari
Affiliations
Weili Miao
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA; Corresponding author
Douglas F. Porter
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA
Zurab Siprashvili
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA
Ian D. Ferguson
Program in Cancer Biology, Stanford University, Stanford, CA, USA
Luca Ducoli
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA
Duy T. Nguyen
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA
Lisa A. Ko
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA
Vanessa Lopez-Pajares
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA
Suhas Srinivasan
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA
Audrey W. Hong
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA
Yen-Yu Yang
Department of Chemistry, University of California, Riverside, Riverside, CA, USA
Zhongwen Cao
Department of Chemistry, University of California, Riverside, Riverside, CA, USA
Robin M. Meyers
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA
Jordan M. Meyers
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA
Shiying Tao
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA
Yinsheng Wang
Department of Chemistry, University of California, Riverside, Riverside, CA, USA
Paul A. Khavari
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA; Program in Cancer Biology, Stanford University, Stanford, CA, USA; Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA; Corresponding author
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.
