title: An alternative mode of microRNA target recognition.
abstract: MicroRNAs (miRNAs) regulate mRNA targets through perfect pairing with their seed region (positions 2-7). Recently, a precise genome-wide map of miRNA interaction sites in mouse brain was generated by high-throughput sequencing and analysis of clusters of ~50-nucleotide mRNA tags cross-linked to Argonaute (Ago HITS-CLIP). By analyzing Ago HITS-CLIP 'orphan clusters'-Ago binding regions from HITS-CLIP that cannot be explained by canonical seed matches-we have now identified an alternative binding mode used by miRNAs. Specifically, G-bulge sites (positions 5-6) are often bound and regulated by miR-124 in brain. More generally, bulged sites comprise ≥15% of all Ago-miRNA interactions in mouse brain and are evolutionarily conserved. We call position 6 the 'pivot' nucleotide and suggest a model in which a transitional 'nucleation bulge' leads to functional bulge mRNA-miRNA interactions, expanding the number of potential miRNA regulatory sites.
authors.affiliation: Laboratory of Neuro-Oncology, The Rockefeller University, Howard Hughes Medical Institute, New York, New York, USA. swchi@skku.edu
authors.forename: Sung Wook
authors.initials: SW
authors.lastname: Chi
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
authors.forename: Robert B
authors.initials: RB
authors.lastname: Darnell
mesh_terms: D020029:Base Pairing; D001665:Binding Sites; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008957:Models, Genetic
chemical_list: D035683:MicroRNAs