miRNA–target chimeras reveal miRNA 3′-end pairing as a major determinant of Argonaute target specificity
Year: 2015
Type: article
Abstract: microRNAs (miRNAs) act as sequence-specific guides for Argonaute (AGO) proteins, which mediate posttranscriptional silencing of target messenger RNAs. Despite their importance in many biological processes, rules governing AGO-miRNA targeting are only partially understood. Here we report a modified AGO HITS-CLIP strategy termed CLEAR (covalent ligation of endogenous Argonaute-bound RNAs)-CLIP, which enriches miRNAs ligated to their endogenous mRNA targets. CLEAR-CLIP mapped ∼130,000 endogenous miRNA-target interactions in mouse brain and ∼40,000 in human hepatoma cells. Motif and structural analysis define expanded pairing rules for over 200 mammalian miRNAs. Most interactions combine seed-based pairing with distinct, miRNA-specific patterns of auxiliary pairing. At some regulatory sites, this specificity confers distinct silencing functions to miRNA family members with shared seed sequences but divergent 3'-ends. This work provides a means for explicit biochemical identification of miRNA sites in vivo, leading to the discovery that miRNA 3'-end pairing is a general determinant of AGO binding specificity.
Source: Nature Communications
DOI: 10.1038/ncomms9864
Authors: Michael J. Moore, Troels K. H. Scheel, Joseph M. Luna, Christopher Y. Park, John J. Fak, Eiko Nishiuchi, Charles M. Rice, Robert B. Darnell
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Howard Hughes Medical Institute, Simons Foundation, Jane Coffin Childs Memorial Fund for Medical Research, Starr Foundation, Simons Foundation Autism Research Initiative, Danmarks Frie Forskningsfond, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke
Awards: Mapping the mechanisms of protein synthesis-dependent synaptic plasticity, Type I interferon-stimulated genes and the antiviral immune response, Modeling human hepatotropic infections in complex tissue organoids, Simianizing hepatitis C: Defining the species-tropism of a hepatotropic virus, Structure and function of the HCV RNA replicase, Neurology and the molecular role of N-RBPs in the brain, A systematic analysis of small RNA interactions during RNA virus infections, Neurology and the molecular role of N-RBPs in the brain, G7764722451, G8379645478, G9000252022
OpenAlex ID: W2180388440