Transcriptome-wide discovery of microRNA binding sites in human brain

Neuron. 2014 Jan 22;81(2):294-305. doi: 10.1016/j.neuron.2013.10.062. Epub 2014 Jan 2.


The orchestration of brain function requires complex gene regulatory networks that are modulated, in part, by microRNAs (miRNAs). These noncoding RNAs associate with argonaute (Ago) proteins in order to direct posttranscriptional gene suppression via base pairing with target transcripts. In order to better understand how miRNAs contribute to human-specialized brain processes and neurological phenotypes, identifying their targets is of paramount importance. Here, we address the latter by profiling Ago2:RNA interactions using HITS-CLIP to generate a transcriptome-wide map of miRNA binding sites in human brain. We uncovered ∼ 7,000 stringent Ago2 binding sites that are highly enriched for conserved sequences corresponding to abundant brain miRNAs. This interactome points to functional miRNA:target pairs across >3,000 genes and represents a valuable resource for accelerating our understanding of miRNA functions in brain. We demonstrate the utility of this map for exploring clinically relevant miRNA binding sites that may facilitate the translation of genetic studies of complex neuropsychiatric diseases into therapeutics.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Animals
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • Autoradiography
  • Base Sequence
  • Binding Sites / genetics*
  • Gene Regulatory Networks
  • Gyrus Cinguli / metabolism*
  • Humans
  • Immunoprecipitation
  • Male
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Middle Aged
  • Motor Cortex / cytology
  • Motor Cortex / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Postmortem Changes
  • RNA, Messenger
  • Transcriptome / physiology


  • Argonaute Proteins
  • MicroRNAs
  • Nerve Tissue Proteins
  • RNA, Messenger

Associated data

  • GEO/GSE52084