Characterization of spindle-E: a protein involved in guarding the genome

Abstract

Transposable selfish genetic elements (TSE) account for a large percentage of the human genome, as well as the genomes of most other organisms. When active, TSEs can transpose (excise and insert) within the genome. Dysregulation of TSEs results in accumulation of DNA double strand breaks, a high rate of mutation, chromosomal rearrangements, and sterility. Silencing of TSEs in the germline has been attributed to a specialized class of small, non-coding RNAs, named Piwi-interacting RNA (piRNA). Drosophila spindle-E (spnE) has been identified as a central component of the piRNA pathway. SpnE is conserved and is necessary for the generation of most ovarian piRNAs in Drosophila and mouse. Both the SpnE and mouse TDRD9 proteins contain a DExH box helicase domain and a Tudor domain and are required for TE silencing and germline development. Through the analysis of several new mutant spnE alleles, we show that the highly conserved DExH box helicase region is required for proper piRNA pathway function. We also show that mutations in the helicase region lead to the formation of Dynein motor complex aggregates as well as the mislocalization of the piRNA binding protein Aubergine (Aub).