MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms

Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9779-84. doi: 10.1073/pnas.1630797100. Epub 2003 Aug 5.

Abstract

MicroRNAs (miRNAs) are endogenously encoded small noncoding RNAs, derived by processing of short RNA hairpins, that can inhibit the translation of mRNAs bearing partially complementary target sequences. In contrast, small interfering RNAs (siRNAs), which are derived by processing of long double-stranded RNAs and are often of exogenous origin, degrade mRNAs bearing fully complementary sequences. Here, we demonstrate that an endogenously encoded human miRNA is able to cleave an mRNA bearing fully complementary target sites, whereas an exogenously supplied siRNA can inhibit the expression of an mRNA bearing partially complementary sequences without inducing detectable RNA cleavage. These data suggest that miRNAs and siRNAs can use similar mechanisms to repress mRNA expression and that the choice of mechanism may be largely or entirely determined by the degree of complementary of the RNA target.

Publication types

  • Comparative Study

MeSH terms

  • Base Sequence
  • Cell Line
  • Gene Expression
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Plasmids / genetics
  • Protein Biosynthesis
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism*
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism*
  • Transfection

Substances

  • MicroRNAs
  • RNA, Messenger
  • RNA, Small Interfering
  • Luciferases