Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, Japan.
PLoS Genet. 2024 Jul 26;20(7):e1011367. doi: 10.1371/journal.pgen.1011367. eCollection 2024 Jul.
The pathway for axon regeneration in Caenorhabditis elegans is activated by SVH-1, a growth factor belonging to the HGF/plasminogen family. SVH-1 is a dual-function factor that acts as an HGF-like growth factor to promote axon regeneration and as a protease to regulate early development. It is important to understand how SVH-1 is converted from a protease to a growth factor for axon regeneration. In this study, we demonstrate that cytidine deaminase (CDD) SVH-17/CDD-2 plays a role in the functional conversion of SVH-1. We find that the codon exchange of His-755 to Tyr in the Asp-His-Ser catalytic triad of SVH-1 can suppress the cdd-2 defect in axon regeneration. Furthermore, the stem hairpin structure around the His-755 site in svh-1 mRNA is required for the activation of axon regeneration by SVH-1. These results suggest that CDD-2 promotes axon regeneration by transforming the function of SVH-1 from a protease to a growth factor through modification of svh-1 mRNA.
秀丽隐杆线虫中轴突再生的途径被 SVH-1 激活，SVH-1 是一种生长因子，属于 HGF/纤溶酶原家族。SVH-1 是一种双功能因子，既作为 HGF 样生长因子促进轴突再生，又作为蛋白酶调节早期发育。了解 SVH-1 如何从蛋白酶转化为轴突再生的生长因子非常重要。在这项研究中，我们证明了胞苷脱氨酶（CDD）SVH-17/CDD-2 在 SVH-1 的功能转换中发挥作用。我们发现 SVH-1 的 Asp-His-Ser 催化三联体中的 His-755 到 Tyr 的密码子交换可以抑制 cdd-2 在轴突再生中的缺陷。此外，svh-1 mRNA 中 His-755 位点周围的茎环结构对于 SVH-1 激活轴突再生是必需的。这些结果表明，CDD-2 通过修饰 svh-1 mRNA 将 SVH-1 的功能从蛋白酶转化为生长因子，从而促进轴突再生。
