Layered-up regulation in the developing brain

Abstract

Modification of messenger RNAs through a process called m⁶A methylation facilitates dynamic temporal regulation of RNA levels in neural precursor cells, enabling fine-tuning of developing neuronal circuits in the brain.

Figure 1. Two layers of transcriptional regulation in the mouse cortex

The addition of methyl groups to DNA can lead to the modulation of gene-transcription levels (different levels indicated by size of arrow). Epigenetic regulatory mechanisms such as this, or chromosome packaging (not shown), which direct patterns of gene expression appropriate to a given cell type, are important in brain development. Yoon et al. now demonstrate that development of the cortex of the embryonic mouse brain can also be regulated by the methylation of messenger RNA — specifically, of a nitrogen atom in the mRNA nucleoside adenosine. This m⁶A methylation reduces the half-lives of mRNAs, causing rapid decay of those involved in developmental regulatory pathways in neuronal precursor cells called radial glia. Such regulation is essential for precisely timed cell divisions and differentiation of radial glia, and so for normal cortical development.