Microprocessor activity controls differential miRNA biogenesis In Vivo

Cell Rep. 2014 Oct 23;9(2):542-54. doi: 10.1016/j.celrep.2014.09.007. Epub 2014 Oct 9.


In miRNA biogenesis, pri-miRNA transcripts are converted into pre-miRNA hairpins. The in vivo properties of this process remain enigmatic. Here, we determine in vivo transcriptome-wide pri-miRNA processing using next-generation sequencing of chromatin-associated pri-miRNAs. We identify a distinctive Microprocessor signature in the transcriptome profile from which efficiency of the endogenous processing event can be accurately quantified. This analysis reveals differential susceptibility to Microprocessor cleavage as a key regulatory step in miRNA biogenesis. Processing is highly variable among pri-miRNAs and a better predictor of miRNA abundance than primary transcription itself. Processing is also largely stable across three cell lines, suggesting a major contribution of sequence determinants. On the basis of differential processing efficiencies, we define functionality for short sequence features adjacent to the pre-miRNA hairpin. In conclusion, we identify Microprocessor as the main hub for diversified miRNA output and suggest a role for uncoupling miRNA biogenesis from host gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HeLa Cells
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA Processing, Post-Transcriptional*
  • RNA-Binding Proteins / metabolism*
  • Ribonuclease III / metabolism*
  • Transcriptome


  • DGCR8 protein, human
  • MicroRNAs
  • RNA-Binding Proteins
  • DROSHA protein, human
  • Ribonuclease III