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Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
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RNA-modifying proteins as anticancer drug targets.

P Ann Boriack-Sjodin1, Scott Ribich1, Robert A Copeland1

  • 1Accent Therapeutics, Inc., Cambridge, MA, USA.

Nature Reviews. Drug Discovery
|May 19, 2018
PubMed
Summary

Epitranscriptomics, or RNA modifications, affect RNA stability and translation. Altered epitranscriptomic mechanisms are implicated in human diseases, including cancer, presenting new therapeutic targets.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • Enzyme-catalyzed covalent modifications impact biological macromolecules like DNA, RNA, proteins, and lipids.
  • RNA modifications, termed epitranscriptomics, influence RNA stability and protein translation.
  • Aberrant epitranscriptomic mechanisms are increasingly linked to human diseases, notably cancer.

Purpose of the Study:

  • To review the current understanding of RNA modifications, focusing on messenger RNA (mRNA) methylation.
  • To highlight the potential roles of epitranscriptomic mechanisms in various cancer types.
  • To discuss RNA-modifying proteins as potential therapeutic targets.

Main Methods:

  • Literature review of epitranscriptomics and its role in disease.

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  • Focus on mRNA methylation and its functional consequences.
  • Analysis of emerging data on RNA-modifying proteins in cancer.

    • Main Results:

    • RNA modifications significantly affect RNA structure, function, and stability.
    • Epitranscriptomic alterations are observed in human cancers and other diseases.
    • mRNA methylation is a key epitranscriptomic mechanism with implications in cancer.

    Conclusions:

    • Epitranscriptomics plays a crucial role in regulating gene expression and cellular function.
    • Dysregulation of epitranscriptomic pathways is associated with human pathologies, particularly cancer.
    • Targeting RNA-modifying proteins offers a promising avenue for novel cancer therapies.