A length-dependent evolutionarily conserved pathway controls nuclear export of circular RNAs

Genes Dev. 2018 May 1;32(9-10):639-644. doi: 10.1101/gad.314856.118. Epub 2018 May 17.


Circular RNAs (circRNAs) are generated from many protein-coding genes. Most accumulate in the cytoplasm, but how circRNA localization or nuclear export is controlled remains unclear. Using RNAi screening, we found that depletion of the Drosophila DExH/D-box helicase Hel25E results in nuclear accumulation of long (>800-nucleotide), but not short, circRNAs. The human homologs of Hel25E similarly regulate circRNA localization, as depletion of UAP56 (DDX39B) or URH49 (DDX39A) causes long and short circRNAs, respectively, to become enriched in the nucleus. These data suggest that the lengths of mature circRNAs are measured to dictate the mode of nuclear export.

Keywords: DDX39A; DDX39B; Hel25E; UAP56; URH49; circRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics*
  • Amino Acid Sequence
  • Amino Acids / genetics
  • Animals
  • Cell Line
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Drosophila Proteins / genetics
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Evolution, Molecular
  • Genetic Variation
  • HeLa Cells
  • Humans
  • Protein Transport / genetics
  • RNA / genetics*
  • RNA / metabolism*
  • RNA, Circular


  • Amino Acids
  • Drosophila Proteins
  • RNA, Circular
  • RNA
  • Hel25E protein, Drosophila
  • DDX39A protein, human
  • DDX39B protein, human
  • DEAD-box RNA Helicases