Exon-intron circular RNAs regulate transcription in the nucleus

Nat Struct Mol Biol. 2015 Mar;22(3):256-64. doi: 10.1038/nsmb.2959. Epub 2015 Feb 9.


Noncoding RNAs (ncRNAs) have numerous roles in development and disease, and one of the prominent roles is to regulate gene expression. A vast number of circular RNAs (circRNAs) have been identified, and some have been shown to function as microRNA sponges in animal cells. Here, we report a class of circRNAs associated with RNA polymerase II in human cells. In these circRNAs, exons are circularized with introns 'retained' between exons; we term them exon-intron circRNAs or EIciRNAs. EIciRNAs predominantly localize in the nucleus, interact with U1 snRNP and promote transcription of their parental genes. Our findings reveal a new role for circRNAs in regulating gene expression in the nucleus, in which EIciRNAs enhance the expression of their parental genes in cis, and highlight a regulatory strategy for transcriptional control via specific RNA-RNA interaction between U1 snRNA and EIciRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Exons / physiology
  • Gene Expression Regulation*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Introns / physiology
  • Models, Genetic
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / metabolism
  • RNA, Untranslated / chemistry*
  • RNA, Untranslated / physiology
  • Sequence Analysis, RNA


  • RNA, Untranslated
  • RNA Polymerase II

Associated data

  • GEO/GSE64443