Subcellular targeting and local translation of mRNAs are critical for axon development. As a class of non-coding small RNA molecules, microRNAs (miRNAs), has been revealed to regulate mRNA stability and translation and to play important roles in a variety processes including the development of the nervous system. However, the functions and mechanisms of axonal miRNAs in the development of axons in primary sensory neurons require investigation.
WANG Bin, PAN Lin and their colleagues, under the supervision of Dr. BAO Lan at the Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences, CAS, found that axon-enriched miR-181d affected axon elongation by locally targeting the mRNAs of microtubule-associated protein 1B (MAP1B) and calmodulin. They further demonstrated that FMRP was associated with miR-181d and its targets MAP1B mRNA (Map1b) and calmodulin mRNA (Calm1). The downregulation of FMRP in Fmr1I304N mice or in the cell bodies of cultured DRG neurons impaired the axonal delivery of miR-181d with Map1b and Calm1, leading to decreased protein levels of MAP1B and calmodulin in axons. Furthermore, nerve growth factor (NGF) increased the local synthesis of MAP1B and calmodulin in axons by releasing Map1b and Calm1 from FMRP and miR-181d-repressing granules. These findings reveal a mechanism for axon elongation by the FMRP-mediated axon delivery of miR-181d and its associated mRNAs and local regulation of protein synthesis.
This work entitled “FMRP-Mediated Axonal Delivery of miR-181d Regulates Axon Elongation by Locally Targeting Map1b and Calm1” was published online in Cell Reports on Dec 17, 2015. This work was collaborated with Drs. JIANG Xingyu and ZHANG Xu.
This Study was supported by the grants from the National Natural Science Foundation of China, the Ministry of Science and Technology of China, China Postdoctoral Science Foundation, Postdoctoral Foundation from Shanghai Institutes for Biological Sciences and Shanghai Postdoctoral Science Foundation.
AUTHOR CONTACT:
BAO Lan, Principal Investigator
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Shanghai, China
Phone: 86-21-54921369;
E-mail: baolan@sibcb.ac.cn
Figure. A model for axon elongation by FMRP-mediated axonal delivery of miR-181d and its associated mRNAs and local regulation of protein synthesis
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