Circular RNA translation: novel protein isoforms and clinical significance

Trends Mol Med. 2022 May;28(5):405-420. doi: 10.1016/j.molmed.2022.03.003. Epub 2022 Apr 2.

Abstract

In recent years, significant attention has focused on circular RNA (circRNA) translation to determine its clinical significance. Cap-independent translation of circRNAs driven by an internal ribosome entry site (IRES) or an N6-methyladenosine (m6A)-containing short sequence is different from the canonical cap-dependent translation of linear mRNAs. New proteins or isoforms possessing novel physiological roles can be generated from translatable circRNAs. The present review describes the elements involved in circRNA translation, and the functions of the translated novel protein isoforms in human diseases. Bifunctional characteristics of translatable circRNAs exerted by the circRNAs and the translated proteins are also discussed. Furthermore, various molecular strategies that could be used as appropriate therapeutic options are proposed.

Keywords: circRNA translation; circular RNA; disease modulation; rolling translation; targeting translation; therapy; translational inhibition.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation
  • Humans
  • Internal Ribosome Entry Sites / genetics
  • Protein Biosynthesis*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA / genetics
  • RNA / metabolism
  • RNA, Circular* / genetics

Substances

  • Internal Ribosome Entry Sites
  • Protein Isoforms
  • RNA, Circular
  • RNA