Heterotypic piRNA Ping-Pong requires qin, a protein with both E3 ligase and Tudor domains
Department of Biochemistry and Molecular Pharmacology; Program in Bioinformatics and Integrative Biology; Program in Molecular Medicine
Medical Subject Headings
Animals; Argonaute Proteins; Cell Nucleus; Computational Biology; DNA Damage; DNA Transposable Elements; Drosophila Proteins; Drosophila melanogaster; Female; Fertility; *Gene Silencing; *Genome, Insect; Membrane Transport Proteins; Mutation; Oocytes; Ovary; Peptide Initiation Factors; Protein Structure, Tertiary; RNA Cleavage; RNA, Small Interfering; RNA-Induced Silencing Complex; Signal Transduction; Ubiquitin-Protein Ligases
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.
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Citation: Mol Cell. 2011 Nov 18;44(4):572-84. doi: 10.1016/j.molcel.2011.10.011. Link to article on publisher's site