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An alternative mode of microRNA target recognition | Nature Structural & Molecular Biology
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MicroRNAs are thought to repress mRNA targets through perfect pairing with their seed region, but a sizeable number of miRNA interaction sites are orphans, without a perfect canonical miRNA partner. Now a large number of miRNAs are found to use an alternative binding mode that involves the bulging out of an unpaired mRNA nucleotide, leading to a functional mRNA-miRNA interaction. 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
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headline:An alternative mode of microRNA target recognition
description:MicroRNAs are thought to repress mRNA targets through perfect pairing with their seed region, but a sizeable number of miRNA interaction sites are orphans, without a perfect canonical miRNA partner. Now a large number of miRNAs are found to use an alternative binding mode that involves the bulging out of an unpaired mRNA nucleotide, leading to a functional mRNA-miRNA interaction. MicroRNAs (miRNAs) regulate mRNA targets through perfect pairing with their seed region (positions 2â7). 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'âAgo binding regions from HITS-CLIP that cannot be explained by canonical seed matchesâwe have now identified an alternative binding mode used by miRNAs. Specifically, G-bulge sites (positions 5â6) are often bound and regulated by miR-124 in brain. More generally, bulged sites comprise â¥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.
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headline:An alternative mode of microRNA target recognition
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