Epitranscriptome-Mediated Regulation of Neuronal Translation.

Abstract

Epitranscriptomic modification of RNA is an important layer of regulation for gene expression. RNA modifications come in many flavors and generate a complex tapestry of a regulatory network. Here, we focus on two major RNA modifications, one on rRNA (2'O Methylation) and another on mRNA (N⁶-Methyladenosine [m⁶A]) and their impact on translation. The 2'O methyl group addition on the ribose sugar of rRNA plays a critical role in RNA folding, ribosome assembly, and its interaction with many RNA binding proteins. Differential methylation of these sites contributes to ribosome heterogeneity and generates potential "specialized ribosomes." Specialized ribosomes are proposed to play a variety of important roles in maintaining pluripotency, lineage specification, and compartmentalized and activity-mediated translation in neurons. The m⁶A modification, on the other hand, determines the stability, transport, and translation of subclasses of mRNA. The dynamic nature of m⁶A owing to the localization and activity of its writers, readers, and erasers makes it a powerful tool for spatiotemporal regulation of translation. While substantial information has accumulated on the nature and abundance of these modifications, their functional consequences are still understudied. In this article, we review the literature constructing the body of our understanding of these two modifications and their outcome on the regulation of translation in general and their impact on the nervous system in particular. We also explore the possibility of how these modifications may collaborate in modulating translation and provoke the thought to integrate the functions of multiple epitranscriptome modifications.