Format

Send to

Choose Destination
Sci Rep. 2017 Nov 21;7(1):15895. doi: 10.1038/s41598-017-16291-8.

RNA metabolism is the primary target of formamide in vivo.

Author information

1
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide/Consejo Superior de Investigaciones Científicas, Carretera de Utrera Km1, 41013, Seville, Spain.
2
Research Department of Genetics, Evolution and Environment and UCL Institute of Healthy Ageing, University College London, WC1E 6BT, London, United Kingdom.
3
School of Health, Sport and Biosciences, University of East London, E15 4LZ, London, United Kingdom.
4
Department of Human Genetics, McGill University, Montreal, H3A 0C7, Quebec, Canada.
5
Human Brain Mapping Unit, Instituto Pluridisciplinar, Universidad Complutense de Madrid, 28040, Madrid, Spain.
6
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide/Consejo Superior de Investigaciones Científicas, Carretera de Utrera Km1, 41013, Seville, Spain. valvtal@upo.es.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center