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  2. Loss of RNA-Binding Protein HuR Leads to Defective Ependymal Cells and Hydrocephalus

Loss of RNA-Binding Protein HuR Leads to Defective Ependymal Cells and Hydrocephalus

  • J Neurosci. 2022 Jan 12;42(2):202-219. doi: 10.1523/JNEUROSCI.1317-21.2021.
Xiu Han 1 2 Xuning Shen 1 2 Min Wang 1 Xin Wang 3 Youli Jian 1 Chonglin Yang 3 Weixiang Guo 4 2
Affiliations

Affiliations

  • 1 State Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
  • 2 Graduate School, University of Chinese Academy of Sciences, Beijing 100093, China.
  • 3 State Key Laboratory of Natural Resource Conservation and Utilization in Yunnan, Center for Life Science, School of Life Sciences, Yunnan University, Kunming 650021, China.
  • 4 State Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China wxguo@genetics.ac.cn.
Abstract

Multiciliated ependymal cells line the ventricle wall and generate CSF flow through ciliary beating. Defects in ependymal cells cause hydrocephalus; however, there are still significant gaps in our understanding the molecular, cellular and developmental mechanisms involved in the pathogenesis of hydrocephalus. Here, we demonstrate that specific deletion of RNA-binding protein (RBP) Hu antigen R (HuR) in the mouse brain results in hydrocephalus and causes postnatal death. HuR deficiency leads to impaired ependymal cell development with defective motile ciliogenesis in both female and male mice. Transcriptome-wide analysis reveals that HuR binds to mRNA transcripts related to ciliogenesis, including cilia and flagella associated protein 52 (Cfap52), the effector gene of Foxj-1 and Rfx transcriptional factors. HuR deficiency accelerates the degradation of Cfap52 mRNA, while overexpression of Cfap52 is able to promote the development of HuR-deficient ependymal cells. Taken together, our results unravel the important role of HuR in posttranscriptional regulation of ependymal cell development by stabilizing Cfap52 mRNA.SIGNIFICANCE STATEMENT This study identifies Hu antigen R (HuR) as a genetic factor involved in the pathogenesis of hydrocephalus. Mechanistically, HuR regulates ependymal cell differentiation and ciliogenesis through stabilizing Cfap52 mRNA, the effector gene of Foxj-1 and Rfx transcriptional factors.

Keywords

HuR; ependymal cell; hydrocephalus.

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