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