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<p>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<sup>2+</sup> 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.</p>

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Guanidine aptamers are present in vertebrate RNAs associated with calcium signaling and neuromuscular function

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月9日

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  • Kumari Kavita,
  • Aya Narunsky,
  • Jessica J. Mohsen,
  • Isha Mahadeshwar,
  • Michael G. Mohsen,
  • Yu-Shin Chang,
  • Ronald R. Breaker

摘要

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 Ca2+ 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.