Ago HITS-CLIP decodes miRNA-mRNA interaction maps

By S. Chi, Julie B Zang, Aldo Mele, R. Darnell. Nature, 2009

1,028 citations recorded by the source corpus.

MicroRNAs (miRNAs) have critical roles in the regulation of gene expression; however, as miRNA activity requires base pairing with only 6-8 nucleotides of messenger RNA, predicting target mRNAs is a major challenge. Recently, high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) has identified functional protein–RNA interaction sites. Here we use HITS-CLIP to covalently crosslink native argonaute (Ago, also called Eif2c) protein–RNA complexes in mouse brain. This produced two simultaneous data sets—Ago–miRNA and Ago–mRNA binding sites—that were combined with bioinformatic analysis to identify interaction sites between miRNA and target mRNA. We validated genome-wide interaction maps for miR-124, and generated additional maps for the 20 most abundant miRNAs present in P13 mouse brain. Ago HITS-CLIP provides a general platform for exploring the specificity and range of miRNA action in vivo, and identifies precise sequences for targeting clinically relevant miRNA–mRNA interactions.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c18cd5fb2ab868dcf5901008dccf4624d7a621e4

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Citations in the corpus

MicroRNA Functions in Stress Responses (2010, positive): “In addition, it has become increasingly evident that miRNA binding sites, although commonly discovered and examined in the 30 untranslated regions, can also be present in the coding sequences (Chi et al., 2009; Hafner et al., 2010; Zisoulis et al., 2010).”
A majority of m6A residues are in the last exons, allowing the potential for 3′ UTR regulation (2015, methodology): “The binding sites in the 3′ UTRs for several other brainproteins known to bind pre-mRNAs and the 3′ UTRs of mRNAs were not enriched for m6A sites.”
Functional microRNA targets in protein coding sequences (2012, positive): “HITS-CLIP data: the HITS-CLIP data are downloaded from the Supplementary Material of Chi et al. (2009). miRNA sequences: the miRNAs used are downloaded from miRBase build 13.”
A ceRNA hypothesis: the Rosetta stone of a hidden RNA language? (2011, background): “Importantly, microRNAs also regulate lncRNAs, as shown in a recent global analysis of Argonaute (Ago)-bound transcripts through the HITS-CLIP technique (Chi et al., 2009; Licatalosi et al., 2008).”