Mutations in RNA methylating enzymes in disease

Abstract

RNA methylation is an abundant modification identified in various RNA species in both prokaryotic and eukaryotic organisms. However, the functional roles for the majority of these methylations remain largely unclear. In eukaryotes, many RNA methylations have been suggested to participate in fundamental cellular processes. Mutations in eukaryotic RNA methylating enzymes, and a consequent change in methylation, often lead to the development of diseases and disorders. In contrast, loss of RNA methylation in prokaryotes can be beneficial to microorganisms, especially under antibiotic pressure. Here we discuss several recent advances in understanding mutational landscape of both eukaryotic and prokaryotic RNA methylating enzymes and their relevance to disease and antibiotic resistance.

The roles of DNA, RNA and histone methylation in ageing and cancer

“…Overall, the key principles of the methylation pathways, in terms of location and regulation of DNA templated processes, are highly conserved throughout mammals. Indeed, their importance is underscored by the fact that disruption of these processes, through inherited or acquired mutations in the main protagonists, results in embryonic lethality or can produce severe disease states [1][2][3][4][5] . Mutations related to developmental diseases have been well described in the literature and the major mutational targets are listed in Supplementary Table 1.…”

“…They co-operate with dedicated "erasers" and "readers" -the protein machinery that removes or recognizes these methylation marks. The importance of the various methylation pathways is highlighted by the fact that their dysregulation is linked to many diseases [1][2][3][4][5] .…”

Biomarker Discovery in Attention Deficit Hyperactivity Disorder: RNA sequencing of Whole Blood in Discordant Twin and Case-Controlled Cohorts

“…ALKBH6 (↑2.8X twins) is potentially important because, while relatively little is known about it, by analogy to its homolog ALKBH5, it is likely to function as a methyl-N6-adenosine (m6A) demethylase [67]. While there are extensive investigations into DNA modifications, such as CpG methylation, as a mode of genetic regulation, a quickly escalating literature suggests that defects in RNA modifications are a contributing factor in neurodevelopmental [68], and other disorders [69].…”

Enhancing Epitranscriptome Module Detection from m6A-Seq Data Using Threshold-Based Measurement Weighting Strategy

“…It has been shown that m 6 A demethylase ALKBH5 maintains the tumorigenicity of glioblastoma stem-like cells by programming cell proliferation [ 19 ]; the m 6 A demethylase FTO plays as an oncogene in Acute Myeloid Leukemia [ 20 ]; and the m 6 A methyltransferase METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells [ 21 ]. Mutations of the RNA methylation enzymes are linked to colon cancer and endometrial cancer [ 22 ]. Due to the importance of RNA m 6 A modification to biological regulation and health, it is of crucial importance and increasing interest to study how the epitranscriptome is shaped to regulate relevant biological processes.…”