Kavita Kumari, Narunsky Aya, Mohsen Jessica J, Mahadeshwar Isha, Mohsen Michael G, Chang Yu-Shin, Breaker Ronald R
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, 06511, USA.
Department of Chemistry, Yale University, New Haven, CT, 06511, USA.
Nat Commun. 2025 Aug 9;16(1):7362. doi: 10.1038/s41467-025-62815-6.
Guanidine is a protein denaturant that is a widely used constituent in explosives, plastics, and resins. Its effects on muscle contraction were initially reported in 1876, which eventually led to the use of guanidine as a treatment for certain ataxia symptoms such as those caused by Lambert-Eaton disease. However, its mechanisms of therapeutic action remained unknown. Guanidine was recently found to be a widespread natural metabolite through the discovery of four bacterial riboswitch classes that selectively recognize this compound. Here, we report the discovery and biochemical validation of vertebrate members of guanidine-I and -II riboswitch aptamer classes that are associated with numerous genes relevant to neuromuscular function, mostly involved in Ca transport or signaling. These findings suggest that guanidine is a widely used signaling molecule that serves as an additional layer of regulation of genes relevant to neuromuscular disorders.
胍是一种蛋白质变性剂，是炸药、塑料和树脂中广泛使用的成分。其对肌肉收缩的影响最初于1876年被报道，这最终导致胍被用于治疗某些共济失调症状，如由兰伯特-伊顿病引起的症状。然而，其治疗作用机制仍然未知。最近，通过发现四类选择性识别该化合物的细菌核糖开关，发现胍是一种广泛存在的天然代谢物。在这里，我们报告了胍-I和-II核糖开关适体类脊椎动物成员的发现及其生化验证，这些成员与许多与神经肌肉功能相关的基因有关，主要参与钙转运或信号传导。这些发现表明，胍是一种广泛使用的信号分子，作为与神经肌肉疾病相关基因的额外调控层。
