Determinants of targeting by endogenous and exogenous microRNAs and siRNAs

Cydney B. Nielsen, Noam Shomron, Rickard Sandberg, Eran Hornstein, Jacob Kitzman, Christopher B. Burge*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Vertebrate mRNAs are frequently targeted for post-transcriptional repression by microRNAs (miRNAs) through mechanisms involving pairing of 3′ UTR seed matches to bases at the 5′ end of miRNAs. Through analysis of expression array data following miRNA or siRNA overexpression or inhibition, we found that mRNA fold change increases multiplicatively (i.e., log-additively) with seed match count and that a single 8 mer seed match mediates down-regulation comparable to two 7 mer seed matches. We identified several targeting determinants that enhance seed match-associated mRNA repression, including the presence of adenosine opposite miRNA base 1 and of adenosine or uridine opposite miRNA base 9, independent of complementarity to the siRNA/miRNA. Increased sequence conservation in the ∼50 bases 5′ and 3′ of the seed match and increased AU content 3′ of the seed match were each independently associated with increased mRNA down-regulation. All of these determinants are enriched in the vicinity of conserved miRNA seed matches, supporting their activity in endogenous miRNA targeting. Together, our results enable improved siRNA off-target prediction, allow integrated ranking of conserved and nonconserved miRNA targets, and show that targeting by endogenous and exogenous miRNAs/siRNAs involves similar or identical determinants. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish
Pages (from-to)1894-1910
Number of pages17
Issue number11
StatePublished - Nov 2007
Externally publishedYes


  • Dicer knockout
  • Mouse embryonic fibroblast
  • RNAi
  • Target prediction
  • miR


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