Stability of miRNA 5'terminal and seed regions is correlated with experimentally observed miRNA-mediated silencing efficacy

Sci Rep. 2012;2:996. doi: 10.1038/srep00996. Epub 2012 Dec 18.

Abstract

MicroRNAs (miRNAs) are key regulators of sequence-specific gene silencing. However, crucial factors that determine the efficacy of miRNA-mediated target gene silencing are poorly understood. Here we mathematized base-pairing stability and showed that miRNAs with an unstable 5' terminal duplex and stable seed-target duplex exhibit strong silencing activity. The results are consistent with the previous findings that an RNA strand with unstable 5' terminal in miRNA duplex easily loads onto the RNA-induced silencing complex (RISC), and miRNA recognizes target mRNAs with seed-complementary sequences to direct posttranscriptional repression. Our results suggested that both the unwinding and target recognition processes of miRNAs could be proficiently controlled by the thermodynamics of base-pairing in protein-free condition. Interestingly, such thermodynamic parameters might be evolutionarily well adapted to the body temperatures of various species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthropods
  • Base Pairing
  • Base Sequence
  • Body Temperature
  • Chickens
  • Databases, Genetic
  • Dogs
  • Gene Silencing*
  • Genes, Reporter
  • HeLa Cells
  • Horses
  • Humans
  • Mice
  • MicroRNAs / chemistry
  • MicroRNAs / metabolism*
  • Plasmids / genetics
  • Plasmids / metabolism
  • RNA Stability
  • RNA-Induced Silencing Complex / metabolism
  • Thermodynamics

Substances

  • MicroRNAs
  • RNA-Induced Silencing Complex