Conformational Dynamics of mRNA in Gene Expression as New Pharmaceutical Target

Chem Rec. 2017 Sep;17(9):817-832. doi: 10.1002/tcr.201700016. Epub 2017 May 17.

Abstract

Gene expression involves concurrent and consecutive events of unidirectional nature, such as transcription occurring from 5' to 3' end and translation from N to C terminus. Recent functional studies have shown the importance of kinetically coupled nucleic acid folding events that influence gene expression processes. For example, mRNA conformational dynamics during transcription and translation regulate gene expression and subsequent protein functionalization. The structure, stability, and kinetic properties of nucleic acids are sensitive to the intracellular molecular environment and can be regulated by using artificially developed molecules. Here, we review our current understanding of how mRNA conformational dynamics affect the consecutive and concurrent processes involved in gene expression and discuss how novel pharmaceutical agents designed to influence RNA conformational dynamics, could be developed to treat various diseases.

Keywords: RNA conformational dynamics; central dogma; co-transcriptional RNA folding; co-translational protein folding; molecular crowding.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Discovery
  • G-Quadruplexes
  • Gene Expression
  • Humans
  • Nucleic Acid Conformation
  • Pharmaceutical Preparations / chemistry*
  • Pharmaceutical Preparations / metabolism
  • Proteins / metabolism
  • RNA Folding
  • RNA, Messenger / chemistry*
  • RNA, Messenger / metabolism
  • Ribosomes / chemistry
  • Ribosomes / metabolism

Substances

  • Pharmaceutical Preparations
  • Proteins
  • RNA, Messenger