A Heterochromatin-Specific RNA Export Pathway Facilitates piRNA Production

Cell. 2019 Aug 8;178(4):964-979.e20. doi: 10.1016/j.cell.2019.07.007.

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.

Keywords: Crm1; Drosophila germline; NXF proteins; RNA export; RNA surveillance; UAP56; heterochromatin; piRNA cluster; piRNA pathway; transposon control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology*
  • Animals
  • Animals, Genetically Modified
  • Argonaute Proteins / metabolism
  • Cell Line
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • DEAD-box RNA Helicases / metabolism
  • DNA Transposable Elements
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism*
  • Gene Silencing
  • Germ Cells / metabolism
  • Heterochromatin / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Karyopherins / metabolism
  • Nucleocytoplasmic Transport Proteins / metabolism*
  • RNA, Small Interfering / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Transcription, Genetic

Substances

  • Argonaute Proteins
  • Boot protein, Drosophila
  • DNA Transposable Elements
  • Drosophila Proteins
  • Heterochromatin
  • Intracellular Signaling Peptides and Proteins
  • Karyopherins
  • Nucleocytoplasmic Transport Proteins
  • Nxf3 protein, Drosophila
  • Nxt1 protein, Drosophila
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Receptors, Cytoplasmic and Nuclear
  • exportin 1 protein
  • Hel25E protein, Drosophila
  • DEAD-box RNA Helicases