Significance of the seed sequence in miRNA regulation
Usually, the nucleotides, 2-7nt in the 5’ end of microRNAs have complementary nucleotide sequence, called seed match sequence in the 3’UTR of the target mRNA. Based on the degree of complementarity, the binding sites in the mRNA are classified as canonical (perfect match) and non-canonical sites (imperfect match).55 While a perfect complementarity between miRNA and target seed sequence results in immediate mRNA decay, partial complementary can lead to translation repression and/or mRNA degradation (Fig. 2 ). It is well-known that the extent of complementarity dictates the affinity for miRNA and mRNA interaction and hence influences the miRNAs’ inhibition efficacy.55–58 miRNAs inhibit mRNAs at an higher extent with a perfect seed matching, however, an imperfect match for seed sequence yields lower efficiency of miRNA mediated target mRNA degradation.55 To investigate the role of seed sequence complementarity in miRNA’s activity, Slutskin et al52 created a range of miRNA regulatory elements (MREs) of varying base-pair complementarity for ten miRNAs in K562 cells52 and reported similar observation as made by Agarwal et al.55 Development of miRNA sequence databases and high throughput assays to measure miRNA and target abundance led to computational models that can accurately predict the extent of pairing and its effect on miRNA repression activity.55,56