Neurons are highly polarized cells extending long axons to their targets to form functional circuits. Subcellular targeting and local translation of mRNAs are critical for axon path?nding, guidance, elongation and survival. Our previous studies suggest that some small non-coding RNAs, microRNAs, localized in the axon regulate local translation of mRNAs, therefore affecting axon branching and elongation (Wang et al., Cell Reports, 2015; Wang & Bao, J Mol Cell Biol, 2017). As another class of non-coding RNA with length exceeding 200 nucleotides, lncRNAs show remarkable tissue specificity and are highly enriched in the brain and nerves. Although many studies indicate prominent roles of lincRNAs for development of nervous system, the distribution, function and mechanism of lncRNAs within axons still remain unclear.
This work entitled “Axon-enriched lincRNA ALAE is required for axon elongation via regulation of local mRNA translation” was published online in Cell Reports on May 4, 2021. WEI Manyi, HUANG Jiansong and his colleagues, under the supervision of Dr. BAO Lan at the Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences and Dr. WANG Bin at Shanghai Research Center for Brian Science and Brain-Inspired Intelligence, found that lincRNA ALAE was enriched in the axons of dorsal root ganglion (DRG) neurons. ALAE was further demonstrated to act through its AU-rich elements (AREs) to prevent the interaction and translational repression of KHSRP on Gap43 mRNA, thereby inhibiting the local translation of GAP43 as well as subsequent axon elongation. This work reveals a spatiotemporally regulatory role of axon-enriched lncRNA on mRNA local translation during axon development.
This work was collaborated with Drs. YANG Li, CHENG Hong, JIANG Xingyu and ZHANG Xu.
A proposed model for ALAE required for axon elongation by regulating the repression of KHSRP on Gap43 mRNA translation