eLife (Jun 2021)
5'-UTR SNP of FGF13 causes translational defect and intellectual disability
- Xingyu Pan,
- Jingrong Zhao,
- Zhiying Zhou,
- Jijun Chen,
- Zhenxing Yang,
- Yuxuan Wu,
- Meizhu Bai,
- Yang Jiao,
- Yun Yang,
- Xuye Hu,
- Tianling Cheng,
- Qianyun Lu,
- Bin Wang,
- Chang-Lin Li,
- Ying-Jin Lu,
- Lei Diao,
- Yan-Qing Zhong,
- Jing Pan,
- Jianmin Zhu,
- Hua-Sheng Xiao,
- Zi-Long Qiu,
- Jinsong Li,
- Zefeng Wang,
- Jingyi Hui,
- Lan Bao,
- Xu Zhang
Affiliations
- Xingyu Pan
- ORCiD
- Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; Shanghai Brain-Intelligence Project Center, Shanghai, China
- Jingrong Zhao
- Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
- Zhiying Zhou
- Shanghai Clinical Center, Chinese Academy of Sciences/Xu-Hui Central Hospital, Shanghai, China
- Jijun Chen
- Shanghai Brain-Intelligence Project Center, Shanghai, China
- Zhenxing Yang
- Shanghai Clinical Center, Chinese Academy of Sciences/Xu-Hui Central Hospital, Shanghai, China
- Yuxuan Wu
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
- Meizhu Bai
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
- Yang Jiao
- School of Life Science and Technology, Shanghai Tech University, Shanghai, China
- Yun Yang
- CAS-MPG Partner Institute for Computational Biology, Chinese Academy of Sciences, Shanghai, China
- Xuye Hu
- Shanghai Brain-Intelligence Project Center, Shanghai, China; Shanghai Clinical Center, Chinese Academy of Sciences/Xu-Hui Central Hospital, Shanghai, China
- Tianling Cheng
- Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
- Qianyun Lu
- CAS-MPG Partner Institute for Computational Biology, Chinese Academy of Sciences, Shanghai, China
- Bin Wang
- Shanghai Brain-Intelligence Project Center, Shanghai, China; State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
- Chang-Lin Li
- Shanghai Brain-Intelligence Project Center, Shanghai, China; Shanghai Clinical Center, Chinese Academy of Sciences/Xu-Hui Central Hospital, Shanghai, China
- Ying-Jin Lu
- Shanghai Brain-Intelligence Project Center, Shanghai, China; Shanghai Clinical Center, Chinese Academy of Sciences/Xu-Hui Central Hospital, Shanghai, China
- Lei Diao
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
- Yan-Qing Zhong
- Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
- Jing Pan
- Shanghai Brain-Intelligence Project Center, Shanghai, China
- Jianmin Zhu
- Shanghai Clinical Center, Chinese Academy of Sciences/Xu-Hui Central Hospital, Shanghai, China
- Hua-Sheng Xiao
- Shanghai Clinical Center, Chinese Academy of Sciences/Xu-Hui Central Hospital, Shanghai, China
- Zi-Long Qiu
- Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
- Jinsong Li
- ORCiD
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
- Zefeng Wang
- CAS-MPG Partner Institute for Computational Biology, Chinese Academy of Sciences, Shanghai, China
- Jingyi Hui
- State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
- Lan Bao
- ORCiD
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; School of Life Science and Technology, Shanghai Tech University, Shanghai, China
- Xu Zhang
- ORCiD
- Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; Shanghai Brain-Intelligence Project Center, Shanghai, China; Shanghai Clinical Center, Chinese Academy of Sciences/Xu-Hui Central Hospital, Shanghai, China; School of Life Science and Technology, Shanghai Tech University, Shanghai, China; Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China
- DOI
- https://doi.org/10.7554/eLife.63021
- Journal volume & issue
-
Vol. 10
Abstract
The congenital intellectual disability (ID)-causing gene mutations remain largely unclear, although many genetic variations might relate to ID. We screened gene mutations in Chinese Han children suffering from severe ID and found a single-nucleotide polymorphism (SNP) in the 5′-untranslated region (5′-UTR) of fibroblast growth factor 13 (FGF13) mRNA (NM_001139500.1:c.-32c>G) shared by three male children. In both HEK293 cells and patient-derived induced pluripotent stem cells, this SNP reduced the translation of FGF13, which stabilizes microtubules in developing neurons. Mice carrying the homologous point mutation in 5′-UTR of Fgf13 showed delayed neuronal migration during cortical development, and weakened learning and memory. Furthermore, this SNP reduced the interaction between FGF13 5′-UTR and polypyrimidine-tract-binding protein 2 (PTBP2), which was required for FGF13 translation in cortical neurons. Thus, this 5′-UTR SNP of FGF13 interferes with the translational process of FGF13 and causes deficits in brain development and cognitive functions.
Keywords
- Intellectual disability
- fibroblast growth factor 13
- single-nucleotide polymorphism
- 5'-untranslated region
- protein translation
- polypyrimidine-tract-binding protein 2