Identification of piRNA Binding Sites Reveals the Argonaute Regulatory Landscape of the C.  elegans Germline

Publication date: Available online 15 February 2018 Source:Cell Author(s): En-Zhi Shen, Hao Chen, Ahmet R. Ozturk, Shikui Tu, Masaki Shirayama, Wen Tang, Yue-He Ding, Si-Yuan Dai, Zhiping Weng, Craig C. Mello 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. Graphical abstract Teaser Transcriptome-wide profiling of piRNA targeting rules provides new insights into the interplay between Argonaute pathways and their p...
Source: Cell - Category: Cytology Source Type: research