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

Wei，Manyi1,3; Huang，Jiansong1,3,4; Li，Guo Wei3,5; Jiang，Bowen1,3; Cheng，Hong3,6; Liu，Xiaoyan7; Jiang，Xingyu7; Zhang，Xu2,3,8; Yang，Li3,5; Bao，Lan1,3,4; Wang，Bin1,2

2021-05-04

10.1016/j.celrep.2021.109053

Cell Reports   影响因子和分区

2211-1247

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.

axon elongation axon-enriched lincRNA GAP43 KHSRP local translation

SCI

英语

其他

WOS:000647423700001

2-s2.0-85105053614

Scopus

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
2.Shanghai Research Center for Brian Science and Brain-Inspired Intelligence,Shanghai,China
3.University of Chinese Academy of Sciences,Beijing,China
4.School of Life Science and Technology,ShanghaiTech University,Shanghai,China
5.CAS Key Laboratory of Computational Biology,Shanghai Institute of Nutrition and Health,Chinese Academy of Sciences,Shanghai,China
6.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
7.Southern University of Science and Technology,Shenzhen,China
8.Shanghai Advanced Research Institute,Chinese Academy of Sciences,Shanghai,China

Wei，Manyi,Huang，Jiansong,Li，Guo Wei,et al. Axon-enriched lincRNA ALAE is required for axon elongation via regulation of local mRNA translation[J]. Cell Reports,2021,35(5).

Wei，Manyi.,Huang，Jiansong.,Li，Guo Wei.,Jiang，Bowen.,Cheng，Hong.,...&Wang，Bin.(2021).Axon-enriched lincRNA ALAE is required for axon elongation via regulation of local mRNA translation.Cell Reports,35(5).

Wei，Manyi,et al."Axon-enriched lincRNA ALAE is required for axon elongation via regulation of local mRNA translation".Cell Reports 35.5(2021).