Pre-mRNA structures forming circular RNAs

Justin R. Welden, Stefan Stamm

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations


Circular RNAs are a recently discovered class of RNAs formed by covalently linking the 5' and 3' end of an RNA. Pre-mRNAs generate circular RNAs through a back-splicing mechanism. Whereas in linear splicing a 5' splice site is connected to a downstream 3' splice site, in back-splicing the 5' splice site is connected to an upstream 3' splice site. Both mechanisms use the spliceosome for catalysis. For back-splicing to occur, the back-splice sites must frequently be brought into close proximity, which is achieved through the formation of secondary structures in the pre-mRNA. In general, these pre-mRNA structures are formed by RNA base pairing between complementary sequences flanking the back-splicing sites. Proteins can abolish these RNA structures through binding to one of the complementary strands. However, proteins can also promote back-splicing without strong RNA structures through multimerization after binding to intronic regions flanking circular exons. In humans, Alu-elements comprising around 11% of the human genome are the best-characterized elements generating structures promoting circular RNA formation. Thus, intronic pre-mRNA structures contribute to the formation of circular RNAs.

Original languageEnglish
Article number194410
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Issue number11-12
StatePublished - Nov 1 2019

Bibliographical note

Publisher Copyright:
© 2019 Elsevier B.V.


  • Alu element
  • Back-splicing
  • Circular RNAs
  • RNA structure

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics


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