The emerging importance of METTL5-mediated ribosomal RNA methylation

The study of the epitranscriptome has thus far focused largely on mRNA methylation. Recent human genetics studies suggest that methylation of ribosomal RNA also contributes to brain development and cognition. In particular, the m⁶A modification at the A-1832 position of the 18S rRNA is installed by METTL5. Mutations or deletions of Mettl5 in humans and mice, respectively, cause abnormal translation and gene expression that in turn mediates stem cell behaviors such as differentiation. In this review, we provide an overview of the current knowledge of the methyltransferase METTL5, as well as the molecular biology surrounding m⁶A on rRNA and how it regulates cell behavior.