Minotaur is critical for primary piRNA biogenesis

• Published in: RNA (Cambridge) 2013-08, Vol.19 (8), p.1064-1077
• Main Authors: Vagin, Vasily V, Yu, Yang, Jankowska, Anna, Luo, Yicheng, Wasik, Kaja A, Malone, Colin D, Harrison, Emily, Rosebrock, Adam, Wakimoto, Barbara T, Fagegaltier, Delphine, Muerdter, Felix, Hannon, Gregory J
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Animals, Genetically Modified; Argonaute Proteins - genetics; Argonaute Proteins - metabolism; Catalytic Domain; DNA Transposable Elements - genetics; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Female; Genes, Insect; Glycerol-3-Phosphate O-Acyltransferase - genetics; Glycerol-3-Phosphate O-Acyltransferase - metabolism; Male; Molecular Sequence Data; Mutation; Phospholipids - metabolism; RNA, Small Interfering - biosynthesis; RNA, Small Interfering - genetics; Signal Transduction
• ISSN: 1355-8382; 1469-9001
• DOI: 10.1261/rna.039669.113

Piwi proteins and their associated small RNAs are essential for fertility in animals. In part, this is due to their roles in guarding germ cell genomes against the activity of mobile genetic elements. piRNA populations direct Piwi proteins to silence transposon targets and, as such, form a molecular code that discriminates transposons from endogenous genes. Information ultimately carried by piRNAs is encoded within genomic loci, termed piRNA clusters. These give rise to long, single-stranded, primary transcripts that are processed into piRNAs. Despite the biological importance of this pathway, neither the characteristics that define a locus as a source of piRNAs nor the mechanisms that catalyze primary piRNA biogenesis are well understood. We searched an EMS-mutant collection annotated for fertility phenotypes for genes involved in the piRNA pathway. Twenty-seven homozygous sterile strains showed transposon-silencing defects. One of these, which strongly impacted primary piRNA biogenesis, harbored a causal mutation in CG5508, a member of the Drosophila glycerol-3-phosphate O-acetyltransferase (GPAT) family. These enzymes catalyze the first acylation step on the path to the production of phosphatidic acid (PA). Though this pointed strongly to a function for phospholipid signaling in the piRNA pathway, a mutant form of CG5508, which lacks the GPAT active site, still functions in piRNA biogenesis. We have named this new biogenesis factor Minotaur.