Epitranscriptomic Modifications Modulate Normal and Pathological Functions in CNS

Transl Stroke Res. 2022 Feb;13(1):1-11. doi: 10.1007/s12975-021-00927-z. Epub 2021 Jul 5.

Abstract

RNA is more than just a combination of four genetically encoded nucleobases as it carries extra information in the form of epitranscriptomic modifications. Diverse chemical groups attach covalently to RNA to enhance the plasticity of cellular transcriptome. The reversible and dynamic nature of epitranscriptomic modifications allows RNAs to achieve rapid and context-specific gene regulation. Dedicated cellular machinery comprising of writers, erasers, and readers drives the epitranscriptomic signaling. Epitranscriptomic modifications control crucial steps of mRNA metabolism such as splicing, export, localization, stability, degradation, and translation. The majority of the epitranscriptomic modifications are highly abundant in the brain and contribute to activity-dependent gene expression. Thus, they regulate the vital physiological processes of the brain, such as synaptic plasticity, neurogenesis, and stress response. Furthermore, epitranscriptomic alterations influence the progression of several neurologic disorders. This review discussed the molecular mechanisms of epitranscriptomic regulation in neurodevelopmental and neuropathological conditions with the goal to identify novel therapeutic targets.

Keywords: 5-Methylcytosine; Brain; Inosine; N1-Methyladenosine; N6-Methyladenosine; Pseudouridine; RNA modifications; Stroke.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Epigenesis, Genetic* / genetics
  • Gene Expression Regulation
  • Neuronal Plasticity / physiology
  • RNA* / genetics
  • RNA* / metabolism
  • Transcriptome / genetics

Substances

  • RNA