A Heterochromatin-Specific RNA Export Pathway Facilitates piRNA Production

Mostafa F. ElMaghraby, Peter Refsing Andersen, Florian Pühringer, Ulrich Hohmann, Katharina Meixner, Thomas Lendl, Laszlo Tirian, Julius Brennecke

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

PIWI-interacting RNAs (piRNAs) guide transposon silencing in animals. The 22–30 nt piRNAs are processed in the cytoplasm from long non-coding RNAs that often lack RNA processing hallmarks of export-competent transcripts. By studying how these transcripts achieve nuclear export, we uncover an RNA export pathway specific for piRNA precursors in the Drosophila germline. This pathway requires Nxf3-Nxt1, a variant of the hetero-dimeric mRNA export receptor Nxf1-Nxt1. Nxf3 interacts with UAP56, a nuclear RNA helicase essential for mRNA export, and CG13741/Bootlegger, which recruits Nxf3-Nxt1 and UAP56 to heterochromatic piRNA source loci. Upon RNA cargo binding, Nxf3 achieves nuclear export via the exportin Crm1 and accumulates together with Bootlegger in peri-nuclear nuage, suggesting that after export, Nxf3-Bootlegger delivers precursor transcripts to the piRNA processing sites. These findings indicate that the piRNA pathway bypasses nuclear RNA surveillance systems to export unprocessed transcripts to the cytoplasm, a strategy also exploited by retroviruses. Heterochromatic piRNA precursors escape classic mRNA quality-control and surveillance mechanisms through a dedicated nuclear export pathway.

Original languageEnglish
Pages (from-to)964-979.e20
JournalCell
Volume178
Issue number4
DOIs
Publication statusPublished - Aug 8 2019

Keywords

  • Crm1
  • Drosophila germline
  • NXF proteins
  • RNA export
  • RNA surveillance
  • UAP56
  • heterochromatin
  • piRNA cluster
  • piRNA pathway
  • transposon control

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    ElMaghraby, M. F., Andersen, P. R., Pühringer, F., Hohmann, U., Meixner, K., Lendl, T., Tirian, L., & Brennecke, J. (2019). A Heterochromatin-Specific RNA Export Pathway Facilitates piRNA Production. Cell, 178(4), 964-979.e20. https://doi.org/10.1016/j.cell.2019.07.007