m6A RNA Methylation: Ramifications for Gene Expression and Human Health
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REVIEW
m6A RNA Methylation: Ramifications for Gene Expression and Human Health R. Karthiya1 · Piyush Khandelia1 Accepted: 14 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Cellular transcriptomes are frequently adorned by a variety of chemical modification marks, which in turn have a profound influence on its functioning. Of these modifications, the one which has invited a lot of attention in the recent years is m6A RNA methylation, leading to the development of RNA epigenetics or epitranscriptomics as a frontier research area. m6A RNA methylation is one of the most abundant reversible internal modification seen in cellular RNAs. Studies in the last few years have not only shed light on the molecular machinery involved in m6A RNA methylation but also on the impact of this modification in regulating gene expression and hence biological processes. In this review, we will emphasize the biological impact of this modification in normal organismal development and diseases. Keywords Transcriptome · Gene regulation · Reversible RNA modifications · m6A RNA methylation
Introduction The flow of genetic information in biological systems from DNA to RNA to protein is explained by the central dogma of molecular biology, which forms the backbone of modern biology [1]. This flow of genetic information is with checks and balances and is often subjected to a wide variety of regulatory controls operational at multiple levels. Adding to this regulatory complexity is the reversible chemical modification of DNA and nucleosomal histones, which are collectively termed as epigenetic marks or signatures. One such well-studied epigenetic modification is DNA methylation, wherein the enzyme DNA methyl transferase adds the methyl group to cytosine in the CpG islands of DNA sequence, leading to transcriptional silencing [2]. The loss of DNA methylation, i.e., hypomethylation has been reported to promote tumorigenicity in various cancer types [3, 4]. Aside from DNA, the tails of nucleosomal histone proteins, which are essential for chromatin formation, are * Piyush Khandelia [email protected]‑pilani.ac.in; [email protected] 1
Department of Biological Sciences, Birla Institute of Technology and Science, Pilani - Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District, Hyderabad, Telangana 500078, India
often subjected to numerous chemical modifications like acetylation, deacetylation, methylation, phosphorylation and ubiquitination [5]. These modifications are catalyzed by specific enzymes, for example, histone acetyl transferase and deacetylase, histone methyl transferase and demethylase facilitate acetylation, deacetylation, methylation and demethylation of histones respectively. Acetylation of histones 3 and 4 at specific amino acid residues, activate transcription by loosening up the chromatin, whereas methylation of histones 3 and 4 at specific positions can activate transcription in certain instances and repress in others [6]. Cellular RNAs, coding as well as
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