Kruppel-like factor 4-dependent Staufen1-mediated mRNA decay regulates cortical neurogenesis

Byoung-San Moon, Jinlun Bai, Mingyang Cai, Chunming Liu, Jiandang Shi and Wange Lu ()
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Byoung-San Moon: University of Southern California
Jinlun Bai: University of Southern California
Mingyang Cai: University of Southern California
Chunming Liu: University of Kentucky
Jiandang Shi: Nankai University
Wange Lu: University of Southern California

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-017-02720-9

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