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

UPF1 is a conserved RNA helicase in eukaryotes which is crucial for the correct expression of nuclear genes. This study presents ChIP-seq evidence indicating its RNA-dependent interaction with mtDNA transcription sites in Drosophila S2 cells. Mitochondrial and frequent co-localisation with nucleoids were validated by immunostaining and GFP-tagging of UPF1 in various fly tissues and cell types. Depletion of UPF1, but not other NMD factors, during spermatogenesis, causes severe meiosis and cytokinesis defects, leading to sterility. RNA-seq indicates that these phenotypes could be primarily due to the reduced expression of genes essential for chromosome segregation. Yet also shows that spermatids depleted of UPF1 exhibit a widespread downregulation of mtDNA transcription and, unlike in wild type, fail to eliminate their mtDNA at the elongation stage. Cumulatively, this study indicates a crucial requirement of UPF1 in the expression of both nuclear and mtDNA genes during spermatogenesis.