RNA modifications and RNA metabolism in neurological disease pathogenesis

Biswanath Chatterjee, Che Kun James Shen, Pritha Majumder

Research output: Contribution to journalReview articlepeer-review

3 Citations (Scopus)

Abstract

The intrinsic cellular heterogeneity and molecular complexity of the mammalian nervous system relies substantially on the dynamic nature and spatiotemporal patterning of gene expression. These features of gene expression are achieved in part through mechanisms involving various epi-genetic processes such as DNA methylation, post-translational histone modifications, and non-coding RNA activity, amongst others. In concert, another regulatory layer by which RNA bases and sugar residues are chemically modified enhances neuronal transcriptome complexity. Similar RNA modifications in other systems collectively constitute the cellular epitranscriptome that integrates and impacts various physiological processes. The epitranscriptome is dynamic and is reshaped constantly to regulate vital processes such as development, differentiation and stress responses. Perturbations of the epitranscriptome can lead to various pathogenic conditions, including cancer, cardiovascular abnormalities and neurological diseases. Recent advances in next-generation sequencing technologies have enabled us to identify and locate modified bases/sugars on different RNA species. These RNA modifications modulate the stability, transport and, most importantly, translation of RNA. In this review, we discuss the formation and functions of some frequently observed RNA modifications—including methylations of adenine and cytosine bases, and isomerization of uridine to pseudouridine—at various layers of RNA metabolism, together with their contributions to ab-normal physiological conditions that can lead to various neurodevelopmental and neurological dis-orders.

Original languageEnglish
Article number11870
JournalInternational journal of molecular sciences
Volume22
Issue number21
DOIs
Publication statusPublished - Nov 2021

Keywords

  • Brain development
  • Neurodegenerative diseases
  • Neurodevelopmental disorders
  • RNA metabolism
  • RNA modifications

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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