Axon-enriched lincRNA ALAE is required for axon elongation via regulation of local mRNA translation
Manyi Wei,
Jiansong Huang,
Guo-Wei Li,
Bowen Jiang,
Hong Cheng,
Xiaoyan Liu,
Xingyu Jiang,
Xu Zhang,
Li Yang,
Lan Bao,
Bin Wang
Affiliations
Manyi Wei
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
Jiansong Huang
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
Guo-Wei Li
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
Bowen Jiang
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
Hong Cheng
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
Xiaoyan Liu
Southern University of Science and Technology, Shenzhen, China
Xingyu Jiang
Southern University of Science and Technology, Shenzhen, China
Xu Zhang
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
Li Yang
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
Lan Bao
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; Corresponding author
Bin Wang
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; Corresponding author
Summary: 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.
