Heterotypic piRNA Ping-Pong requires qin, a protein with both E3 ligase and Tudor domains

Mol Cell. 2011 Nov 18;44(4):572-84. doi: 10.1016/j.molcel.2011.10.011.

Abstract

piRNAs guide PIWI proteins to silence transposons in animal germ cells. Reciprocal cycles of piRNA-directed RNA cleavage--catalyzed by the PIWI proteins Aubergine (Aub) and Argonaute3 (Ago3) in Drosophila melanogaster--expand the population of antisense piRNAs in response to transposon expression, a process called the Ping-Pong cycle. Heterotypic Ping-Pong between Aub and Ago3 ensures that antisense piRNAs predominate. We show that qin, a piRNA pathway gene whose protein product contains both E3 ligase and Tudor domains, colocalizes with Aub and Ago3 in nuage, a perinuclear structure implicated in transposon silencing. In qin mutants, less Ago3 binds Aub, futile Aub:Aub homotypic Ping-Pong prevails, antisense piRNAs decrease, many families of mobile genetic elements are reactivated, and DNA damage accumulates in nurse cells and oocytes. We propose that Qin enforces heterotypic Ping-Pong between Aub and Ago3, ensuring that transposons are silenced and maintaining the integrity of the germline genome.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Computational Biology
  • DNA Damage
  • DNA Transposable Elements / genetics*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Female
  • Fertility
  • Gene Silencing* / physiology
  • Genome, Insect*
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / genetics
  • Mutation
  • Oocytes / cytology
  • Oocytes / metabolism*
  • Ovary / cytology
  • Ovary / metabolism*
  • Peptide Initiation Factors / genetics
  • Peptide Initiation Factors / metabolism
  • Protein Structure, Tertiary / genetics
  • RNA Cleavage
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • RNA-Induced Silencing Complex / genetics*
  • RNA-Induced Silencing Complex / metabolism
  • Signal Transduction
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • AGO3 protein, Drosophila
  • Argonaute Proteins
  • DNA Transposable Elements
  • Drosophila Proteins
  • Membrane Transport Proteins
  • Peptide Initiation Factors
  • RNA, Small Interfering
  • RNA-Induced Silencing Complex
  • aub protein, Drosophila
  • tud protein, Drosophila
  • Qin protein, Drosophila
  • Ubiquitin-Protein Ligases

Associated data

  • GEO/GSE30061