IsomiRs: Expanding the miRNA repression toolbox beyond the seed.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that play increasingly appreciated roles in gene regulation. In animals, miRNAs silence gene expression by binding to partially complementary sequences within target mRNAs. It is well-established that miRNAs recognize canonical target sites by base-pairing in the 5'region. However, the development of biochemical methods has identified many novel, non-canonical target sites, suggesting additional modes of miRNA-target association. Here, we review the current knowledge of miRNA-target recognition and how new evidence supports or challenges existing models. We also review the process by which microRNA isoforms achieve functional diversification via modulation of target recognition. Published by Elsevier B.V.