title: Specificity and functionality of microRNA inhibitors.
abstract: BACKGROUND
  Micro(mi)RNAs regulate gene expression through translational attenuation and messenger (m)RNA degradation, and are associated with differentiation, homeostasis and disease. Natural miRNA target recognition is determined primarily by perfect complementarity in a seed region (nucleotide positions 2 to 7) with additional interactions contributing in a sequence- and target-specific manner. Synthetic miRNA target analogs, which are fully complementary, chemically modified oligonucleotides, have been used successfully to inhibit miRNA function.
  
  
  RESULTS
  In this paper, we present a first systematic study to evaluate the effect of mismatches in the target site on synthetic inhibitor activity. Panels of miRNA inhibitors containing two-nucleotide mismatches across the target site were tested against three miRNAs (miR-21, miR-22 and miR-122). The results showed that the function of inhibitors vary as mismatch positions in the inhibitors change.
  
  
  CONCLUSIONS
  The data indicate that features important for natural miRNA target recognition (such as seed region complementarity) are also important for inhibitor functionality. In addition, base pairing at a second, more 3' region appears to be equally important in determining the efficacy of synthetic inhibitors. Considering the importance of these inhibitor regions and the expression of closely related miRNA sequences will enable researchers to interpret results more accurately in future experiments.
authors.affiliation: Dharmacon Products, Thermo Fisher Scientific, 2650 Crescent Drive, Suite 100 Lafayette, CO 80026, USA. annaleen.vermeulen@thermofisher.com.
authors.forename: Barbara
authors.initials: B
authors.lastname: Robertson
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Dalby
authors.forename: Jon
authors.initials: J
authors.lastname: Karpilow
authors.forename: Anastasia
authors.initials: A
authors.lastname: Khvorova
authors.forename: Devin
authors.initials: D
authors.lastname: Leake
authors.forename: Annaleen
authors.initials: A
authors.lastname: Vermeulen