Differential RISC association of endogenous human microRNAs predicts their inhibitory potential

Omar Flores, Edward M. Kennedy, Rebecca L. Skalsky, Bryan R. Cullen

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


It has previously been assumed that the generally high stability of microRNAs (miRNAs) reflects their tight association with Argonaute (Ago) proteins, essential components of the RNA-induced silencing complex (RISC). However, recent data have suggested that the majority of mature miRNAs are not, in fact, Ago associated. Here, we demonstrate that endogenous human miRNAs vary widely, by >100-fold, in their level of RISC association and show that the level of Ago binding is a better indicator of inhibitory potential than is the total level of miRNA expression. While miRNAs of closely similar sequence showed comparable levels of RISC association in the same cell line, these varied between different cell types. Moreover, the level of RISC association could be modulated by overexpression of complementary target mRNAs. Together, these data indicate that the level of RISC association of a given endogenous miRNA is regulated by the available RNA targetome and predicts miRNA function.

Original languageEnglish (US)
Pages (from-to)4629-4639
Number of pages11
JournalNucleic acids research
Issue number7
StatePublished - Apr 2014
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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