Transcriptome-wide miR-155 binding map reveals widespread noncanonical microRNA targeting

Mol Cell. 2012 Dec 14;48(5):760-70. doi: 10.1016/j.molcel.2012.10.002. Epub 2012 Nov 8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • Binding Sites
  • CD4-Positive T-Lymphocytes / metabolism
  • Computational Biology
  • Down-Regulation
  • Gene Expression Profiling / methods
  • Genes, Reporter
  • HEK293 Cells
  • Humans
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nucleotide Motifs
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Transcriptome*
  • Transfection


  • 3' Untranslated Regions
  • Argonaute Proteins
  • MicroRNAs
  • Mirn155 microRNA, mouse
  • RNA, Messenger

Associated data

  • GEO/GSE41288