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

Kumari Kavita, Aya Narunsky, Jessica J. Mohsen, Isha Mahadeshwar, Michael G. Mohsen, Yu-Shin Chang and Ronald R. Breaker ()
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Kumari Kavita: Yale University
Aya Narunsky: Yale University
Jessica J. Mohsen: Yale University
Isha Mahadeshwar: Yale University
Michael G. Mohsen: Yale University
Yu-Shin Chang: Yale University
Ronald R. Breaker: Yale University

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-62815-6

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