Making ends meet: New functions of mRNA secondary structure

Wiley Interdiscip Rev RNA. 2021 Mar;12(2):e1611. doi: 10.1002/wrna.1611. Epub 2020 Jun 29.


The 5' cap and 3' poly(A) tail of mRNA are known to synergistically regulate mRNA translation and stability. Recent computational and experimental studies revealed that both protein-coding and non-coding RNAs will fold with extensive intramolecular secondary structure, which will result in close distances between the sequence ends. This proximity of the ends is a sequence-independent, universal property of most RNAs. Only low-complexity sequences without guanosines are without secondary structure and exhibit end-to-end distances expected for RNA random coils. The innate proximity of RNA ends might have important biological implications that remain unexplored. In particular, the inherent compactness of mRNA might regulate translation initiation by facilitating the formation of protein complexes that bridge mRNA 5' and 3' ends. Additionally, the proximity of mRNA ends might mediate coupling of 3' deadenylation to 5' end mRNA decay. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems Translation > Translation Regulation.

Keywords: RNA secondary structure; end-to-end distance; translation regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Protein Biosynthesis
  • RNA Stability*
  • RNA*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • RNA, Messenger
  • RNA