UPF1 is required for gene expression in mitochondria and for the elimination of paternal mtDNA

UPF1 is a well-conserved RNA helicase in eukaryotes, involved in nuclear and cytoplasmic processes of gene expression. This study presents ChIP-seq evidence for its RNA-dependent association with mtDNA transcription sites in Drosophila S2 cells, and RNA-seq data indicating its requirement for the correct expression of mtDNA genes. UPF1 localisation in mitochondria was observed by immunostaining and GFP-tagging in different fly tissues and cell types. During spermatogenesis, depletion of UPF1 but not of other NMD factors, resulted in major defects in meiosis and cytokinesis, leading to complete sterility. Notably, the few spermatids produced show abnormalities in the formation of the nebenkern and, unlike the wild type, retain the mtDNA. To investigate transcriptomic changes in salivary gland cells, when depleted of UPF1, UPF2 and UPF3 by UAS induction of shRNA targeting the respective mRNA, and to investigate transcriptomic changes in Drosophila S2 cells, when depleted of UPF1