The RNA-Binding ATPase, Armitage, Couples piRNA Amplification in Nuage to Phased piRNA Production on Mitochondria
RNA Therapeutics Institute; Program in Bioinformatics and Integrative Biology; Graduate School of Biomedical Sciences
Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology | Bioinformatics | Cell and Developmental Biology | Cells | Computational Biology | Enzymes and Coenzymes | Genetic Phenomena | Genetics and Genomics | Integrative Biology | Nucleic Acids, Nucleotides, and Nucleosides | Systems Biology
PIWI-interacting RNAs (piRNAs) silence transposons in Drosophila ovaries, ensuring female fertility. Two coupled pathways generate germline piRNAs: the ping-pong cycle, in which the PIWI proteins Aubergine and Ago3 increase the abundance of pre-existing piRNAs, and the phased piRNA pathway, which generates strings of tail-to-head piRNAs, one after another. Proteins acting in the ping-pong cycle localize to nuage, whereas phased piRNA production requires Zucchini, an endonuclease on the mitochondrial surface. Here, we report that Armitage (Armi), an RNA-binding ATPase localized to both nuage and mitochondria, links the ping-pong cycle to the phased piRNA pathway. Mutations that block phased piRNA production deplete Armi from nuage. Armi ATPase mutants cannot support phased piRNA production and inappropriately bind mRNA instead of piRNA precursors. We propose that Armi shuttles between nuage and mitochondria, feeding precursor piRNAs generated by Ago3 cleavage into the Zucchini-dependent production of Aubergine- and Piwi-bound piRNAs on the mitochondrial surface.
ATP, DTME, RNA-seq, argonaute, helicase, immunoprecipitation, mass spectrometry, microscopy, mitochondrion, small RNA
DOI of Published Version
Mol Cell. 2019 Jun 6;74(5):982-995.e6. doi: 10.1016/j.molcel.2019.04.006. Epub 2019 May 7. Link to article on publisher's site
Ge, Daniel Tianfang; Wang, Wei; Tipping, Cindy; Ildar Gainetdinov; Weng, Zhiping; and Zamore, Phillip D., "The RNA-Binding ATPase, Armitage, Couples piRNA Amplification in Nuage to Phased piRNA Production on Mitochondria" (2019). Program in Bioinformatics and Integrative Biology Publications and Presentations. 151.