title: Noncoding RNA. piRNA-guided slicing specifies transcripts for Zucchini-dependent, phased piRNA biogenesis.
abstract: In animal gonads, PIWI-clade Argonaute proteins repress transposons sequence-specifically via bound Piwi-interacting RNAs (piRNAs). These are processed from single-stranded precursor RNAs by largely unknown mechanisms. Here we show that primary piRNA biogenesis is a 3'-directed and phased process that, in the Drosophila germ line, is initiated by secondary piRNA-guided transcript cleavage. Phasing results from consecutive endonucleolytic cleavages catalyzed by Zucchini, implying coupled formation of 3' and 5' ends of flanking piRNAs. Unexpectedly, Zucchini also participates in 3' end formation of secondary piRNAs. Its function can, however, be bypassed by downstream piRNA-guided precursor cleavages coupled to exonucleolytic trimming. Our data uncover an evolutionarily conserved piRNA biogenesis mechanism in which Zucchini plays a central role in defining piRNA 5' and 3' ends.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohrgasse 3, 1030 Vienna, Austria.
authors.forename: Fabio
authors.initials: F
authors.lastname: Mohn
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohrgasse 3, 1030 Vienna, Austria.
authors.forename: Dominik
authors.initials: D
authors.lastname: Handler
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohrgasse 3, 1030 Vienna, Austria.
authors.forename: Julius
authors.initials: J
authors.lastname: Brennecke
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D005260:Female; D005854:Germ Cells / Q000201:enzymology; D008297:Male; D051379:Mice; D010053:Ovary / Q000201:enzymology; D059367:RNA Cleavage; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics; D013737:Testis / Q000201:enzymology; D014158:Transcription, Genetic; D014529:Uridine / Q000378:metabolism; D000094704:RNA, Guide, CRISPR-Cas Systems
chemical_list: D029721:Drosophila Proteins; D004722:Endoribonucleases; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D014529:Uridine; D000094704:RNA, Guide, CRISPR-Cas Systems; C547123:Tdrkh protein, mouse; C521347:Zuc protein, Drosophila