Versatility of MicroRNA biogenesis

PLoS One. 2011 May 10;6(5):e19391. doi: 10.1371/journal.pone.0019391.

Abstract

MicroRNAs (miRNAs) are short single-stranded RNA molecules that regulate gene expression. MiRNAs originate from large primary (pri) and precursor (pre) transcripts that undergo various processing steps along their biogenesis pathway till they reach their mature and functional form. It is not clear, however, whether all miRNAs are processed similarly. Here we show that the ratio between pre-miRNA and mature miRNA forms varies between different miRNAs. Moreover, over-expression of several factors involved in miRNA biogenesis, including Exportin-5, Drosha, NF90a, NF45 and KSRP, displayed bidirectional effects on pre/mature miRNA ratios, suggesting their intricate biogenesis sensitivity. In an attempt to identify additional factors that might explain the versatility in miRNA biogenesis we have analyzed the contribution of two hnRNP family members, hnRNPH1 and hnRNPR. Knock-down or over-expression of these genes suggested that hnRNPR inhibits, whereas hnRNPH1 facilitates, miRNA processing. Overall, our results emphasize that miRNA biogenesis is versatile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Karyopherins / genetics
  • Karyopherins / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Nuclear Factor 45 Protein / genetics
  • Nuclear Factor 45 Protein / metabolism
  • Nuclear Factor 90 Proteins / genetics
  • Nuclear Factor 90 Proteins / metabolism
  • Polymerase Chain Reaction
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism

Substances

  • ILF2 protein, human
  • ILF3 protein, human
  • KHSRP protein, human
  • Karyopherins
  • MicroRNAs
  • Nuclear Factor 45 Protein
  • Nuclear Factor 90 Proteins
  • RNA-Binding Proteins
  • Trans-Activators
  • XPO5 protein, human
  • DROSHA protein, human
  • Ribonuclease III