Thrown for a (stem) loop: How RNA structure impacts circular RNA regulation and function

Veronica F. Busa, Anthony K.L. Leung

Research output: Contribution to journalArticlepeer-review


Exonic circular RNAs (circRNAs) are RNA molecules that are covalently closed by back-splicing via canonical splicing machinery. Despite overlapping sequences, exon circularization generates RNA secondary structures through intramolecular base-pairing that are different from the linear transcript. Here we review factors that may affect circRNA structure and how structure affects circRNA function and regulation. We highlight considerations for RNA sequencing and expression measurement to ensure highly structured circRNAs are accurately represented by the data and discuss issues that need to be addressed in generating circRNAs to recapitulate their endogenous structures. We conclude our review by discussing experimental strategies on revealing the varied roles of RNA structure in circRNA biogenesis, function and decay.

Original languageEnglish (US)
Pages (from-to)56-67
Number of pages12
StatePublished - Dec 2021


  • Circular RNA
  • RNA secondary structure

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Thrown for a (stem) loop: How RNA structure impacts circular RNA regulation and function'. Together they form a unique fingerprint.

Cite this