轴突富集lincRNA ALAE通过调控局部mRNA翻译促进轴突延伸的机制

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 a previously unappreciated axon-enriched lincRNA regulating axon elongation, thus referred to as ALAE. Profiling of highly expressed lincRNAs detected abundant and enriched ALAE in the axon 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 axon of DRG neurons. Furthermore, local disruption of the interaction between ALAE and KHSRP in the axon significantly inhibited Gap43 mRNA translation, thereby impairing axon elongation. Together, this study implicates crucial roles of axon-enriched lincRNAs in spatiotemporally regulating local translation during axon development.