The m5C reader protein Ybx1 promotes axon growth by regulating local translation in axons.

IF 3.7 2区 生物学 Q1 DEVELOPMENTAL BIOLOGY Development Pub Date : 2024-12-01 Epub Date: 2024-11-29 DOI:10.1242/dev.202781
Jun Yu, Yanbo Zhang, Jian Zhang, Pengfei Che, Gaoxin Long, Zhuoxuan Yang, Sheng-Jian Ji
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Abstract

It has been shown that 5-methylcytosine (m5C), one of the most abundant modifications on RNA, regulates various biological processes. However, the function of m5C modification in the nervous system is still largely unknown. Here, we show that the m5C reader Ybx1 is highly expressed in the developing mouse hippocampus in the central nervous system (CNS). Conditional knockout of Ybx1 in the dentate gyrus (DG) decreases mossy fiber growth and affects short-term memory. In the peripheral nervous system (PNS), the mRNA of Ybx1 is enriched in the axons of dorsal root ganglion (DRG) neurons and can be locally translated. Inhibition of local translation of Ybx1 results in a decrease in axon growth. We further identify 28 target mRNAs of Ybx1 in DRG neurons, including Ttl and Mmp24. Axon-specific knockdown of Ttl and Mmp24 decreases axon growth rate both in DRG and DG. It could be a general mechanism that locally translated Ybx1 regulates axon growth by controlling local translation in both CNS and PNS.

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m5C解读蛋白Ybx1通过调节轴突的局部翻译促进轴突生长。
研究表明,5-甲基胞嘧啶(5-methylcytosine, m5C)是RNA上最丰富的修饰之一,可调控多种生物过程。然而,m5C修饰在神经系统中的作用仍是未知的。在这里,我们发现m5C读取器Ybx1在中枢神经系统(CNS)发育中的小鼠海马中高度表达。条条性敲除齿状回(DG)中的Ybx1会减少苔藓纤维的生长并影响短期记忆。在外周神经系统(PNS)中,Ybx1的mRNA富集于背根神经节(DRG)神经元的轴突,可以局部翻译。抑制Ybx1的局部翻译导致轴突生长减少。我们进一步在DRG神经元中鉴定了28个Ybx1的靶mrna,包括Ttl和Mmp24。轴突特异性敲低Ttl和Mmp24会降低DRG和DG的轴突生长速率。局部翻译的Ybx1通过控制CNS和PNS的局部翻译调节轴突生长可能是一种普遍的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Development
Development 生物-发育生物学
CiteScore
6.70
自引率
4.30%
发文量
433
审稿时长
3 months
期刊介绍: Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community. Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication. To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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