Pre-mRNA structures forming circular RNAs

Biochim Biophys Acta Gene Regul Mech. 2019 Nov-Dec;1862(11-12):194410. doi: 10.1016/j.bbagrm.2019.194410. Epub 2019 Aug 14.

Abstract

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.

Keywords: Alu element; Back-splicing; Circular RNAs; RNA structure.

Publication types

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

MeSH terms

  • Alu Elements
  • Base Pairing
  • Humans
  • Models, Molecular
  • Nucleic Acid Conformation
  • RNA 3' Polyadenylation Signals
  • RNA Precursors / chemistry*
  • RNA Splice Sites
  • RNA Splicing*
  • RNA, Circular / chemistry*
  • Spliceosomes / chemistry
  • Spliceosomes / genetics

Substances

  • RNA Precursors
  • RNA Splice Sites
  • RNA, Circular