Functions and Dynamics of Methylation in Eukaryotic mRNA

Abstract

Eukaryotic messenger RNA (mRNA) contains non-canonical nucleosides, which are modified mostly by methylation. Although some modifications are known for decades, advances in high-throughput sequencing and mass spectrometric techniques now have allowed to elucidate transcriptome wide methylation patterns. The discovery of methyltransferases that write and demethylases that erase methylations in a sequence-specific manner, as well as reader proteins that recognize these modifications leading to a specific biological response, has triggered wide attention converting the research field of mRNA methylation into a current hotspot in molecular biology. Most research has focussed on N6-methyladenosine (m6A), which is the most abundant modification in eukaryotic mRNA. Therefore, this overview has a focus on m6A summarizing the current knowledge on how specific m6A patterns are generated and how they are recognized and translated into biological outputs like alternative splicing, altered transcript stability, or modified translational activity of mRNAs. The distribution patterns of other methylations in mRNA, such as N1-methyladenosine (m1A), 5-methylcytidine (m5C) and 5-hydroxymethylcytidine (hm5C) have also been mapped in recent years. We review the current knowledge regarding these and other minor eukaryotic mRNA methylations and provide an outlook suggesting potential future research directions.