Front Cell Dev Biol
Division of Biomedical and Life Sciences, Lancaster University, Lancaster, United Kingdom.
Published: January 2021
The cellular RNA can acquire a variety of chemical modifications during the cell cycle, and compelling pieces of evidence highlight the importance of these modifications in determining the metabolism of RNA and, subsequently, cell physiology. Among myriads of modifications, methylation at the N6-position of adenosine (mA) is the most important and abundant internal modification in the messenger RNA. The mA marks are installed by methyltransferase complex proteins (writers) in the majority of eukaryotes and dynamically reversed by demethylases such as FTO and ALKBH5 (erasers). The incorporated mA marks on the RNA transcripts are recognized by m6A-binding proteins collectively called readers. Recent epigenetic studies have unequivocally highlighted the association of mA demethylases with a range of biomedical aspects, including human diseases, cancers, and metabolic disorders. Moreover, the mechanisms of demethylation by mA erasers represent a new frontier in the future basic research on RNA biology. In this review, we focused on recent advances describing various physiological, pathological, and viral regulatory roles of mA erasers. Additionally, we aim to analyze structural insights into well-known mA-demethylases in assessing their substrate binding-specificity, efficiency, and selectivity. Knowledge on cellular and viral RNA metabolism will shed light on mA-specific recognition by demethylases and will provide foundations for the future development of efficacious therapeutic agents to various cancerous conditions and open new avenues for the development of antivirals.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835257 | PMC |
http://dx.doi.org/10.3389/fcell.2020.587108 | DOI Listing |
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