​Adv Sci Ji Shengjian's group reveals the molecular mechanism of m6A modification regulating axon growth

m6A is a ubiquitous modification on mRNA, and its modification affects the processes of mRNA shearing, transport, translation, and degradation
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The previous research of Ji Shengjian's group has shown that m6A modification plays an important role in the early neurodevelopment process (Yu et al.
, Nucleic Acids Research, 2018; Zhuang et al.
, Nucleic Acids Research, 2019)
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The eraser protein FTO of m6A regulates axon growth by regulating the local translation of GAP43 mRNA in axons
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In addition, they found that the reader protein YTHDF1 of m6A regulates the process of axon guidance by controlling the translation of Robo3.
1 mRNA
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However, how the m6A reader protein regulates the local translation of mRNA is not yet known
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On October 12, 2021, Ji Shengjian’s group from the School of Life Sciences, Southern University of Science and Technology published an online titled The m6A Readers YTHDF1 and YTHDF2 Synergistically Control Cerebellar Parallel Fiber Growth by Regulating Local Translation of the Key Wnt5a Signaling Components in Axons on Advanced Science.
Research papers
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This study revealed a new mechanism by which the m6A reader protein (reader) regulates the local translation of messenger ribonucleic acid (mRNA) in the axons of cerebellar granule cells, thereby regulating axon growth
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The latest research of Ji Shengjian's group found that the reader proteins YTHDF1 and YTHDF2 of m6A are highly expressed in the axons of mouse cerebellar granule cells
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After knocking down YTHDF1 or YTHDF2, the axon growth of granulosa cells was significantly increased
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Through multi-omics analysis, they found that the key target mRNAs regulated by YTHDF1 and YTHDF2 are Dvl1 and Wnt5a, respectively
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Interestingly, Dvl1 and Wnt5a are key molecules in the Wnt/Planar cell polarity (PCP) signaling pathway
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Further research found that YTHDF1 promotes the local translation of Dvl1 mRNA in axons, and YTHDF2 affects the local translation of Wnt5a mRNA by affecting the stability of Wnt5a mRNA, thereby coordinating the growth of axons
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Figure 1.
YTHDF1 and YTHDF2 coordinately regulate the Wnt5a/PCP signaling pathway to control cerebellar granule cell axon growth.
In addition, after specifically knocking out YTHDF1 or YTHDF2 in mouse cerebellar granule cells, the parallel fibers (axons) of granule cells extend The length is significantly increased
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Surprisingly, the number of synapses formed by the parallel fibers of granule cells and Purkinje cells also increased significantly, which ultimately led to a significant improvement in the motor balance of the conditioned knockout mice
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These studies show that YTHDF1 and YTHDF2 cooperate to negatively regulate the axon growth of cerebellar granule cells under physiological conditions
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Figure 2.
Ythdf1 or Ythdf2 conditional knockout mice have significantly increased parallel fibers and significantly improved exercise balance ability in Ji Shengjian's research group, Yu Jun, PhD student of SUSTech-Hong Kong University Joint Pei, She Yuanchu, a 2019 PhD student of SUSTech, and Yang Lixin, former postdoctoral fellow for the paper The co-first author, Ji Shengjian is the corresponding author
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Ji Shengjian’s group has made a series of important progress in the field of m6A modification and regulation of neurodevelopment and function, so it has recently been specially commissioned to write a related review in Frontiers in Cell and Developmental Biology
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The first author of the review is Yu Jun, She Yuanchu also made important contributions, and Ji Shengjian is the corresponding author
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Original link: AS: https://onlinelibrary.
wiley.
com/doi/10.
1002/advs.
202101329FCDB: https:// Platemaker: Notes for reprinting on the 11th [ Non-original articles] The copyright of this article belongs to the author of the article.
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