TRNA processing defects induce replication stress and Chk2‐dependent disruption of piRNA transcription. (16th October 2015)

• Record Type: Journal Article
• Authors: Molla‐Herman, Anahi; Vallés, Ana Maria; Ganem‐Elbaz, Carine; Antoniewski, Christophe; Huynh, Jean‐René
• Is Part Of: EMBO journal. Volume 34:Number 24(2015)
• Page Start: 3009
• Page End: 3027
• Publication Date: 2015-10-16
• Subjects: Drosophila -- dysgenesis -- heterochromatin -- oogenesis -- transposon; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201591006
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: RNase P is a conserved endonuclease that processes the 5′ trailer of tRNA precursors. We have isolated mutations in Rpp30, a subunit of RNase P, and find that these induce complete sterility in Drosophila females. Here, we show that sterility is not due to a shortage of mature tRNAs, but that atrophied ovaries result from the activation of several DNA damage checkpoint proteins, including p53, Claspin, and Chk2. Indeed, we find that tRNA processing defects lead to increased replication stress and de‐repression of transposable elements in mutant ovaries. We also report that transcription of major piRNA sources collapse in mutant germ cells and that this correlates with a decrease in heterochromatic H3K9me3 marks on the corresponding piRNA‐producing loci. Our data thus link tRNA processing, DNA replication, and genome defense by small RNAs. This unexpected connection reveals constraints that could shape genome organization during evolution. Synopsis: The loss of tRNA endonuclease RNase P causes female sterility in flies by inducing replication stress at tRNA loci, leading to a collapse of piRNA transcription and de‐repression of deleterious transposable elements. This finding reveals a new role for tRNAs in genome stability. Mutation of RNase P subunit Rpp30 leads to viable flies with oogenesis arrested at early stages. Rpp30 mutants show mild defects in tRNA abundance. Rpp30 mutations lead to strong expression of transposable elements. The loss of Rpp30 activates replication stress and DNA damage checkpoints leading to oogenesis arrest and sterility. Rpp30 mutation affects H3K9me3 mark deposition on main piRNAs clusters, thereby affecting piRNA transcription. Abstract : The loss of tRNA endonuclease RNase P causes female sterility in flies by inducing replication stress at tRNA loci, leading to a collapse of piRNA transcription and de‐repression of deleterious transposable elements. This finding reveals a new role for tRNAs in genome stability.