2. Academic Validation
  3. Altered nucleocytoplasmic export of adenosine-rich circRNAs by PABPC1 contributes to neuronal function

Altered nucleocytoplasmic export of adenosine-rich circRNAs by PABPC1 contributes to neuronal function

  • Mol Cell. 2024 Jun 20;84(12):2304-2319.e8. doi: 10.1016/j.molcel.2024.05.011.
Shi-Meng Cao 1,  Hao Wu 1,  Guo-Hua Yuan 2,  Yu-Hang Pan 1,  Jun Zhang 1,  Yu-Xin Liu 1,  Siqi Li 1,  Yi-Feng Xu 1,  Meng-Yuan Wei 1,  Li Yang 3,  Ling-Ling Chen 4
Affiliations

Affiliations

  • 1 Key Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • 2 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Center for Molecular Medicine, Children's Hospital, Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • 3 Center for Molecular Medicine, Children's Hospital, Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • 4 Key Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; New Cornerstone Science Laboratory, Shenzhen 518054, China. Electronic address: linglingchen@sibcb.ac.cn.
PMID: 38838666 DOI: 10.1016/j.molcel.2024.05.011
Abstract

Circular RNAs (circRNAs) are upregulated during neurogenesis. Where and how circRNAs are localized and what roles they play during this process have remained elusive. Comparing the nuclear and cytoplasmic circRNAs between H9 cells and H9-derived forebrain (FB) neurons, we identify that a subset of adenosine (A)-rich circRNAs are restricted in H9 nuclei but exported to cytosols upon differentiation. Such a subcellular relocation of circRNAs is modulated by the poly(A)-binding protein PABPC1. In the H9 nucleus, newly produced (A)-rich circRNAs are bound by PABPC1 and trapped by the nuclear basket protein TPR to prevent their export. Modulating (A)-rich motifs in circRNAs alters their subcellular localization, and introducing (A)-rich circRNAs in H9 cytosols results in mRNA translation suppression. Moreover, decreased nuclear PABPC1 upon neuronal differentiation enables the export of (A)-rich circRNAs, including circRTN4(2,3), which is required for neurite outgrowth. These findings uncover subcellular localization features of circRNAs, linking their processing and function during neurogenesis.

Keywords

PABPC1; TPR; adenosine-rich; circRTN4(2,3); circular RNA; neurite outgrowth; neuronal differentiation; nuclear pore complex; nucleocytoplasmic export.

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