TRBP alters human precursor microRNA processing in vitro

RNA. 2012 Nov;18(11):2012-9. doi: 10.1261/rna.035501.112. Epub 2012 Sep 24.


MicroRNAs play central roles in controlling gene expression in human cells. Sequencing data show that many miRNAs are produced at different levels and as multiple isoforms that can vary in length at their 5' or 3' ends, but the biogenesis and functional significance of these RNAs are largely unknown. We show here that the human trans-activation response (TAR) RNA binding protein (TRBP), a known molecular partner of the miRNA processing enzyme Dicer, changes the rates of pre-miRNA cleavage in an RNA-structure-specific manner. Furthermore, TRBP can trigger the generation of iso-miRNAs (isomiRs) that are longer than the canonical sequence by one nucleotide. We show that this change in miRNA processing site can alter guide strand selection, resulting in preferential silencing of a different mRNA target. These results implicate TRBP as a key regulator of miRNA processing and targeting in humans.

Publication types

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

MeSH terms

  • Base Sequence
  • DEAD-box RNA Helicases / chemistry
  • DEAD-box RNA Helicases / metabolism
  • Genes, Reporter
  • HEK293 Cells
  • Humans
  • Kinetics
  • Luciferases, Renilla / biosynthesis
  • Luciferases, Renilla / genetics
  • MicroRNAs / chemistry*
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • RNA Cleavage
  • RNA Precursors / chemistry*
  • RNA Precursors / metabolism
  • RNA Processing, Post-Transcriptional*
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / metabolism
  • RNA-Binding Proteins / physiology
  • Ribonuclease III / chemistry
  • Ribonuclease III / metabolism
  • Sequence Analysis, RNA
  • Substrate Specificity


  • MicroRNAs
  • RNA Precursors
  • RNA-Binding Proteins
  • trans-activation responsive RNA-binding protein
  • Luciferases, Renilla
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases