2. Academic Validation
  3. Axon-enriched lincRNA ALAE is required for axon elongation via regulation of local mRNA translation

Axon-enriched lincRNA ALAE is required for axon elongation via regulation of local mRNA translation

  • Cell Rep. 2021 May 4;35(5):109053. doi: 10.1016/j.celrep.2021.109053.
Manyi Wei 1,  Jiansong Huang 2,  Guo-Wei Li 3,  Bowen Jiang 1,  Hong Cheng 4,  Xiaoyan Liu 5,  Xingyu Jiang 5,  Xu Zhang 6,  Li Yang 3,  Lan Bao 7,  Bin Wang 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China.
  • 2 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China; School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • 3 University of Chinese Academy of Sciences, Beijing, China; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
  • 4 University of Chinese Academy of Sciences, Beijing, China; State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.
  • 5 Southern University of Science and Technology, Shenzhen, China.
  • 6 Shanghai Research Center for Brian Science and Brain-Inspired Intelligence, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China; Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China.
  • 7 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China; School of Life Science and Technology, ShanghaiTech University, Shanghai, China. Electronic address: baolan@sibcb.ac.cn.
  • 8 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China; Shanghai Research Center for Brian Science and Brain-Inspired Intelligence, Shanghai, China. Electronic address: bin_wang2020@163.com.
PMID: 33951423 DOI: 10.1016/j.celrep.2021.109053
Abstract

Long intergenic noncoding RNAs (lincRNAs) are critical regulators involved in diverse biological processes. However, the roles and related mechanisms of lincRNAs in axon development are largely unknown. Here we report an axon-enriched lincRNA regulating axon elongation, referred to as ALAE. Profiling of highly expressed lincRNAs detected abundant and enriched ALAE in the axons of dorsal root ganglion (DRG) neurons, where it locally promoted axon elongation. Mechanically, ALAE directly interacted with the KH3-4 domains of KH-type splicing regulatory protein (KHSRP) and impeded its association with growth-associated protein 43 (Gap43) mRNA. Knockdown of ALAE reduced the protein but not the mRNA level of GAP43 in the axons of DRG neurons. Furthermore, local disruption of the interaction between ALAE and KHSRP in the axon significantly inhibited Gap43 mRNA translation, impairing axon elongation. This study implies crucial roles of axon-enriched lincRNAs in spatiotemporal regulation of local translation during axon development.

Keywords

GAP43; KHSRP; axon elongation; axon-enriched lincRNA; local translation.

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