Identification of piRNA Binding Sites Reveals the Argonaute Regulatory Landscape of the C. elegans Germline
RNA Therapeutics Institute; Program in Bioinformatics and Integrative Biology
Biochemistry, Biophysics, and Structural Biology | Bioinformatics | Computational Biology
piRNAs (Piwi-interacting small RNAs) engage Piwi Argonautes to silence transposons and promote fertility in animal germlines. Genetic and computational studies have suggested that C. elegans piRNAs tolerate mismatched pairing and in principle could target every transcript. Here we employ in vivo cross-linking to identify transcriptome-wide interactions between piRNAs and target RNAs. We show that piRNAs engage all germline mRNAs and that piRNA binding follows microRNA-like pairing rules. Targeting correlates better with binding energy than with piRNA abundance, suggesting that piRNA concentration does not limit targeting. In mRNAs silenced by piRNAs, secondary small RNAs accumulate at the center and ends of piRNA binding sites. In germline-expressed mRNAs, however, targeting by the CSR-1 Argonaute correlates with reduced piRNA binding density and suppression of piRNA-associated secondary small RNAs. Our findings reveal physiologically important and nuanced regulation of individual piRNA targets and provide evidence for a comprehensive post-transcriptional regulatory step in germline gene expression.
DOI of Published Version
Cell. 2018 Feb 22;172(5):937-951.e18. doi: 10.1016/j.cell.2018.02.002. Epub 2018 Feb 15. Link to article on publisher's site
Shen, En-Zhi; Chen, Hao; Ozturk, Ahmet R.; Tu, Shikui; Shirayama, Masaki; Tang, Wen; Ding, Yue-He; Dai, Si-Yuan; Weng, Zhiping; and Mello, Craig C., "Identification of piRNA Binding Sites Reveals the Argonaute Regulatory Landscape of the C. elegans Germline" (2018). Program in Bioinformatics and Integrative Biology Publications and Presentations. 130.