A Biogenesis Step Upstream of Microprocessor Controls miR-17∼92 Expression

Cell. 2015 Aug 13;162(4):885-99. doi: 10.1016/j.cell.2015.07.008. Epub 2015 Aug 6.


The precise control of miR-17∼92 microRNA (miRNA) is essential for normal development, and overexpression of certain miRNAs from this cluster is oncogenic. Here, we find that the relative expression of the six miRNAs processed from the primary (pri-miR-17∼92) transcript is dynamically regulated during embryonic stem cell (ESC) differentiation. Pri-miR-17∼92 is processed to a biogenesis intermediate, termed "progenitor-miRNA" (pro-miRNA). Pro-miRNA is an efficient substrate for Microprocessor and is required to selectively license production of pre-miR-17, pre-miR-18a, pre-miR-19a, pre-miR-20a, and pre-miR-19b from this cluster. Two complementary cis-regulatory repression domains within pri-miR-17∼92 are required for the blockade of miRNA processing through the formation of an autoinhibitory RNA conformation. The endonuclease CPSF3 (CPSF73) and the spliceosome-associated ISY1 are responsible for pro-miRNA biogenesis and expression of all miRNAs within the cluster except miR-92. Thus, developmentally regulated pro-miRNA processing is a key step controlling miRNA expression and explains the posttranscriptional control of miR-17∼92 expression in development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation
  • Embryonic Stem Cells / metabolism*
  • Endonucleases / metabolism
  • Gene Expression
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • RNA Processing, Post-Transcriptional*
  • Ribonuclease III / metabolism
  • Sequence Alignment
  • Spliceosomes / metabolism


  • MicroRNAs
  • Endonucleases
  • Ribonuclease III