FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment

EMBO J. 2012 Dec 12;31(24):4502-10. doi: 10.1038/emboj.2012.319.


microRNA abundance has been shown to depend on the amount of the microprocessor components or, in some cases, on specific auxiliary co-factors. In this paper, we show that the FUS/TLS (fused in sarcoma/translocated in liposarcoma) protein, associated with familial forms of Amyotrophic Lateral Sclerosis (ALS), contributes to the biogenesis of a specific subset of microRNAs. Among them, species with roles in neuronal function, differentiation and synaptogenesis were identified. We also show that FUS/TLS is recruited to chromatin at sites of their transcription and binds the corresponding pri-microRNAs. Moreover, FUS/TLS depletion leads to decreased Drosha level at the same chromatin loci. Limited FUS/TLS depletion leads to a reduced microRNA biogenesis and we suggest a possible link between FUS mutations affecting nuclear/cytoplasmic partitioning of the protein and altered neuronal microRNA biogenesis in ALS pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation
  • Electrophoretic Mobility Shift Assay
  • Humans
  • Immunoprecipitation
  • MicroRNAs / biosynthesis*
  • Neurons / cytology*
  • Neurons / physiology
  • Oligonucleotides / genetics
  • Plasmids / genetics
  • RNA-Binding Protein FUS / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Ribonuclease III / metabolism*
  • Synapses / genetics
  • Synapses / physiology*


  • Chromatin
  • MicroRNAs
  • Oligonucleotides
  • RNA-Binding Protein FUS
  • DROSHA protein, human
  • Ribonuclease III