Abstract
Kruppel-like factor 4 (Klf4) is a zinc-finger-containing protein that plays a critical role in diverse cellular physiology. While most of these functions attribute to its role as a transcription factor, it is postulated that Klf4 may play a role other than transcriptional regulation. Here we demonstrate that Klf4 loss in neural progenitor cells (NPCs) leads to increased neurogenesis and reduced self-renewal in mice. In addition, Klf4 interacts with RNA-binding protein Staufen1 (Stau1) and RNA helicase Ddx5/17. They function together as a complex to maintain NPC self-renewal. We report that Klf4 promotes Stau1 recruitment to the 3′-untranslated region of neurogenesis-associated mRNAs, increasing Stau1-mediated mRNA decay (SMD) of these transcripts. Stau1 depletion abrogated SMD of target mRNAs and rescued neurogenesis defects in Klf4-overexpressing NPCs. Furthermore, Ddx5/17 knockdown significantly blocked Klf4-mediated mRNA degradation. Our results highlight a novel molecular mechanism underlying stability of neurogenesis-associated mRNAs controlled by the Klf4/Ddx5/17/Stau1 axis during mammalian corticogenesis.
Document Type
Article
Publication Date
1-26-2018
Digital Object Identifier (DOI)
https://doi.org/10.1038/s41467-017-02720-9
Funding Information
The work was supported by National Natural Science Foundation of China Grant 31530027, 31470779 and National Institutes of Health Grant R01 NS067213-01A1. B.-S.M. was supported by postdoctoral fellowship from the California Institute for Regenerative Medicine (CIRM) (No. TG2-01161).
Related Content
Supplementary Information accompanies this paper at https://doi.org/10.1038/s41467-017-02720-9.
Repository Citation
Moon, Byoung-San; Bai, Jinlun; Cai, Mingyang; Liu, Chunming; Shi, Jiandang; and Lu, Wange, "Kruppel-Like Factor 4-Dependent Staufen1-Mediated mRNA Decay Regulates Cortical Neurogenesis" (2018). Molecular and Cellular Biochemistry Faculty Publications. 139.
https://uknowledge.uky.edu/biochem_facpub/139
Supplementary Information
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Cell and Developmental Biology Commons, Genetics and Genomics Commons
Notes/Citation Information
Published in Nature Communications, v. 9, article no. 401, p. 1-15.
© The Author(s) 2018
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