Specificity of microRNA target selection in translational repression

MicroRNAs (miRNAs) are a class of noncoding RNAs found in organisms as evolutionarily distant as plants and mammals, yet most of the mRNAs they regulate are unknown. Here we show that the ability of an miRNA to translationally repress a target mRNA is largely dictated by the free energy of binding of the first eight nucleotides in the 5' region of the miRNA. However, G:U wobble base-pairing in this region interferes with activity beyond that predicted on the basis of thermodynamic stability. Furthermore, an mRNA can be simultaneously repressed by more than one miRNA species. The level of repression achieved is dependent on both the amount of mRNA and the amount of available miRNA complexes. Thus, predicted…

• NI
  National Institutes of Health

  Awards: GM34277, R37-GM34277, P30-CA14051, CA42063
• UP
  U.S. Public Health Service

  Awards: R37-GM34277, P30-CA14051, CA42063
• NC
  National Cancer Institute

  Awards: P30-CA14051, CA14051, CA42063, PO1-CA42063, R37-GM34277