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

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Kumari Kavita, Aya Narunsky, Jessica J. Mohsen, Isha Mahadeshwar, Michael G. Mohsen, Yu-Shin Chang, Ronald R. Breaker
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-62815-6
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849331643750285312
author Kumari Kavita
Aya Narunsky
Jessica J. Mohsen
Isha Mahadeshwar
Michael G. Mohsen
Yu-Shin Chang
Ronald R. Breaker
author_facet Kumari Kavita
Aya Narunsky
Jessica J. Mohsen
Isha Mahadeshwar
Michael G. Mohsen
Yu-Shin Chang
Ronald R. Breaker
author_sort Kumari Kavita
collection DOAJ
description 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.
format Article
id doaj-art-6d5dec121e664e73af421e67c82cdf9d
institution Kabale University
issn 2041-1723
language English
publishDate 2025-08-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-6d5dec121e664e73af421e67c82cdf9d2025-08-20T03:46:28ZengNature PortfolioNature Communications2041-17232025-08-0116111210.1038/s41467-025-62815-6Guanidine aptamers are present in vertebrate RNAs associated with calcium signaling and neuromuscular functionKumari Kavita0Aya Narunsky1Jessica J. Mohsen2Isha Mahadeshwar3Michael G. Mohsen4Yu-Shin Chang5Ronald R. Breaker6Department of Molecular, Cellular and Developmental Biology, Yale UniversityDepartment of Molecular, Cellular and Developmental Biology, Yale UniversityDepartment of Chemistry, Yale UniversityDepartment of Molecular Biophysics and Biochemistry, Yale UniversityDepartment of Molecular, Cellular and Developmental Biology, Yale UniversityDepartment of Molecular, Cellular and Developmental Biology, Yale UniversityDepartment of Molecular, Cellular and Developmental Biology, Yale UniversityAbstract 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.https://doi.org/10.1038/s41467-025-62815-6
spellingShingle Kumari Kavita
Aya Narunsky
Jessica J. Mohsen
Isha Mahadeshwar
Michael G. Mohsen
Yu-Shin Chang
Ronald R. Breaker
Guanidine aptamers are present in vertebrate RNAs associated with calcium signaling and neuromuscular function
Nature Communications
title Guanidine aptamers are present in vertebrate RNAs associated with calcium signaling and neuromuscular function
title_full Guanidine aptamers are present in vertebrate RNAs associated with calcium signaling and neuromuscular function
title_fullStr Guanidine aptamers are present in vertebrate RNAs associated with calcium signaling and neuromuscular function
title_full_unstemmed Guanidine aptamers are present in vertebrate RNAs associated with calcium signaling and neuromuscular function
title_short Guanidine aptamers are present in vertebrate RNAs associated with calcium signaling and neuromuscular function
title_sort guanidine aptamers are present in vertebrate rnas associated with calcium signaling and neuromuscular function
url https://doi.org/10.1038/s41467-025-62815-6
work_keys_str_mv AT kumarikavita guanidineaptamersarepresentinvertebraternasassociatedwithcalciumsignalingandneuromuscularfunction
AT ayanarunsky guanidineaptamersarepresentinvertebraternasassociatedwithcalciumsignalingandneuromuscularfunction
AT jessicajmohsen guanidineaptamersarepresentinvertebraternasassociatedwithcalciumsignalingandneuromuscularfunction
AT ishamahadeshwar guanidineaptamersarepresentinvertebraternasassociatedwithcalciumsignalingandneuromuscularfunction
AT michaelgmohsen guanidineaptamersarepresentinvertebraternasassociatedwithcalciumsignalingandneuromuscularfunction
AT yushinchang guanidineaptamersarepresentinvertebraternasassociatedwithcalciumsignalingandneuromuscularfunction
AT ronaldrbreaker guanidineaptamersarepresentinvertebraternasassociatedwithcalciumsignalingandneuromuscularfunction