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UPF1 is required for gene expression in mitochondria and paternal mtDNA clearance during spermatogenesis

Wright, M. T.; Singh, A. K.; Dixon, H. L.; Price, E. M.; Connolly, E. C.; di Maio, A.; Barlow, J. P.; Catoni, M.; Fan, Y.; Brogna, S.

2024-07-05 cell biology
10.1101/2024.05.10.591322 bioRxiv
Show abstract

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.

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