Slicing and Binding by Ago3 or Aub Trigger Piwi-Bound piRNA Production by Distinct Mechanisms
Program in Bioinformatics and Integrative Biology; Department of Biochemistry and Molecular Pharmacology; RNA Therapeutics Institute
Active Transport, Cell Nucleus; Animals; Argonaute Proteins; DNA Transposable Elements; Drosophila Proteins; Drosophila melanogaster; Female; Gene Silencing; Genes, Insect; Models, Biological; Mutation; Ovum; Peptide Initiation Factors; Protein Binding; RNA Cleavage; RNA, Small Interfering
Biochemistry | Bioinformatics | Computational Biology | Molecular Biology | Molecular Genetics
In Drosophila ovarian germ cells, PIWI-interacting RNAs (piRNAs) direct Aubergine and Argonaute3 to cleave transposon transcripts and instruct Piwi to repress transposon transcription, thereby safeguarding the germline genome. Here, we report that RNA cleavage by Argonaute3 initiates production of most Piwi-bound piRNAs. We find that the cardinal function of Argonaute3, whose piRNA guides predominantly correspond to sense transposon sequences, is to produce antisense piRNAs that direct transcriptional silencing by Piwi, rather than to make piRNAs that guide post-transcriptional silencing by Aubergine. We also find that the Tudor domain protein Qin prevents Aubergine's cleavage products from becoming Piwi-bound piRNAs, ensuring that antisense piRNAs guide Piwi. Although Argonaute3 slicing is required to efficiently trigger phased piRNA production, an alternative, slicing-independent pathway suffices to generate Piwi-bound piRNAs that repress transcription of a subset of transposon families. This alternative pathway may help flies silence newly acquired transposons for which they lack extensively complementary piRNAs.
DOI of Published Version
Mol Cell. 2015 Sep 3;59(5):819-30. doi: 10.1016/j.molcel.2015.08.007. Link to article on publisher's site
Wang, Wei; Han, Bo W.; Tipping, Cindy; Ge, Daniel Tianfang; Zhang, Zhao; Weng, Zhiping; and Zamore, Phillip D., "Slicing and Binding by Ago3 or Aub Trigger Piwi-Bound piRNA Production by Distinct Mechanisms" (2015). Program in Bioinformatics and Integrative Biology Publications and Presentations. 74.