Abstract：
:MicroRNAs (miRNAs) are essential components of gene regulation, but identification of miRNA targets remains a major challenge. Most target prediction and discovery relies on perfect complementarity of the miRNA seed to the 3' untranslated region (UTR). However, it is unclear to what extent miRNAs target sites without seed matches. Here, we performed a transcriptome-wide identification of the endogenous targets of a single miRNA-miR-155-in a genetically controlled manner. We found that approximately 40% of miR-155-dependent Argonaute binding occurs at sites without perfect seed matches. The majority of these noncanonical sites feature extensive complementarity to the miRNA seed with one mismatch. These noncanonical sites confer regulation of gene expression, albeit less potently than canonical sites. Thus, noncanonical miRNA binding sites are widespread, often contain seed-like motifs, and can regulate gene expression, generating a continuum of targeting and regulation.
journal_name
Mol Celljournal_title
Molecular cellauthors
Loeb GB,Khan AA,Canner D,Hiatt JB,Shendure J,Darnell RB,Leslie CS,Rudensky AYdoi
10.1016/j.molcel.2012.10.002subject
Has Abstractpub_date
2012-12-14 00:00:00pages
760-70issue
5eissn
1097-2765issn
1097-4164pii
S1097-2765(12)00854-4journal_volume
48pub_type
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