Functional 5' UTR mRNA structures in eukaryotic translation regulation and how to find them

Nat Rev Mol Cell Biol. 2018 Mar;19(3):158-174. doi: 10.1038/nrm.2017.103. Epub 2017 Nov 22.


RNA molecules can fold into intricate shapes that can provide an additional layer of control of gene expression beyond that of their sequence. In this Review, we discuss the current mechanistic understanding of structures in 5' untranslated regions (UTRs) of eukaryotic mRNAs and the emerging methodologies used to explore them. These structures may regulate cap-dependent translation initiation through helicase-mediated remodelling of RNA structures and higher-order RNA interactions, as well as cap-independent translation initiation through internal ribosome entry sites (IRESs), mRNA modifications and other specialized translation pathways. We discuss known 5' UTR RNA structures and how new structure probing technologies coupled with prospective validation, particularly compensatory mutagenesis, are likely to identify classes of structured RNA elements that shape post-transcriptional control of gene expression and the development of multicellular organisms.

Publication types

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

MeSH terms

  • 5' Untranslated Regions*
  • Animals
  • Eukaryotic Initiation Factor-3 / metabolism
  • Eukaryotic Initiation Factor-4F / metabolism
  • G-Quadruplexes
  • Humans
  • Internal Ribosome Entry Sites
  • Models, Biological
  • Models, Molecular
  • Peptide Chain Initiation, Translational
  • Protein Biosynthesis
  • RNA Folding
  • RNA Helicases / metabolism
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Ribosomes / genetics
  • Ribosomes / metabolism


  • 5' Untranslated Regions
  • Eukaryotic Initiation Factor-3
  • Eukaryotic Initiation Factor-4F
  • Internal Ribosome Entry Sites
  • RNA, Messenger
  • RNA Helicases