RNA metabolism is the primary target of formamide in vivo

Article


Hoyos-Manchado, Rafael, Reyes-Martín, Félix, Rallis, C., Gamero-Estévez, Enrique, Rodríguez-Gómez, Pablo, Quintero-Blanco, Juan, Bähler, Jürg, Jiménez, Juan and Tallada, Víctor A. 2017. RNA metabolism is the primary target of formamide in vivo. Scientific Reports. 7, p. Art: 15895.
AuthorsHoyos-Manchado, Rafael, Reyes-Martín, Félix, Rallis, C., Gamero-Estévez, Enrique, Rodríguez-Gómez, Pablo, Quintero-Blanco, Juan, Bähler, Jürg, Jiménez, Juan and Tallada, Víctor A.
Abstract

The synthesis, processing and function of coding and non-coding RNA molecules and their interacting proteins has been the focus of a great deal of research that has boosted our understanding of key molecular pathways that underlie higher order events such as cell cycle control, development, innate immune response and the occurrence of genetic diseases. In this study, we have found that formamide preferentially weakens RNA related processes in vivo. Using a non-essential Schizosaccharomyces pombe gene deletion collection, we identify deleted loci that make cells sensitive to formamide. Sensitive deletions are significantly enriched in genes involved in RNA metabolism. Accordingly, we find that previously known temperature-sensitive splicing mutants become lethal in the presence of the drug under permissive temperature. Furthermore, in a wild type background, splicing efficiency is decreased and R-loop formation is increased in the presence of formamide. In addition, we have also isolated 35 formamide-sensitive mutants, many of which display remarkable morphology and cell cycle defects potentially unveiling new players in the regulation of these processes. We conclude that formamide preferentially targets RNA related processes in vivo, probably by relaxing RNA secondary structures and/or RNA-protein interactions, and can be used as an effective tool to characterize these processes.

JournalScientific Reports
Journal citation7, p. Art: 15895
ISSN2045-2322
Year2017
PublisherNature Publishing Group
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Digital Object Identifier (DOI)doi:10.1038/s41598-017-16291-8
Web address (URL)https://doi.org/10.1038/s41598-017-16291-8
Publication dates
Online21 Nov 2017
Publication process dates
Deposited28 Nov 2017
Accepted10 Nov 2017
Accepted10 Nov 2017
FunderJosé Castillejo mobility
Grupos emergentes UPO
Wellcome Trust Senior Investigator Award
Spanish Ministerio de Economía y Competitividad
Copyright information© 2017 The authors
LicenseCC BY 4.0
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https://repository.uel.ac.uk/item/849wx

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