RNA nucleotide methylation: 2021 update

Among RNA modifications, transfer of methylgroups from the typical cofactor S-adenosyl-l-methionine by methyltransferases (MTases) to RNA is by far the most common reaction. Since our last review about a decade ago, the field has witnessed the re-emergence of mRNA methylation as an important mechanism in gene regulation. Attention has then spread to many other RNA species; all being included into the newly coined concept of the epitranscriptome. The focus moved from prokaryotes and single cell eukaryotes as model organisms to higher eukaryotes, in particular to mammals. The perception of the field has dramatically changed over the past decade. A previous lack of phenotypes in knockouts in single cell organisms has been replaced by the apparition of MTases in numerous disease models and clinical investigations. Major driving forces of the field include methylation mapping techniques, as well as the characterization of the various MTases, termed writers. The latter term has spilled over from DNA modification in the neighboring epigenetics field, along with the designations readers, applied to mediators of biological effects upon specific binding to a methylated RNA. Furthermore eraser enzymes effect the newly discovered oxidative removal of methylgroups. A sense of reversibility and dynamics has replaced the older perception of RNA modification as a concrete-cast, irreversible part of RNA maturation. A related concept concerns incompletely methylated residues, which, through permutation of each site, lead to inhomogeneous populations of numerous modivariants. This review recapitulates the major developments of the past decade outlined above, and attempts a prediction of upcoming trends. This article is categorized under: RNA Processing > RNA Editing and Modification

Automated summary

RNA methylation has re-emerged as an important mechanism in gene regulation, leading to new insights in RNA research; the presence of methyltransferases in disease models and clinical investigations has significantly contributed to the field's progress; the concept of reversibility and dynamics in RNA modification has replaced the previous perception of irreversible RNA maturation, potentially resulting in diverse populations of RNA variants.