coding and noncoding genes regulated by let-7 familys of microRNAs during mammalian evolution. Homo sapiens; Macaca mulatta; Chlorocebus sabaeus; Rattus norvegicus

MicroRNA (miRNA) family members with paralogous sequences are generally believed to generation by gene duplication events, which play an important role in evolution process. But relatively little is known about the functional divergence of paralogous miRNA genes after duplication, and how the target recognition and repression evolved across species. To address these questions, herein, We transfect hsa-let-7a or hsa-let-7b double strand mimics into four mammal species kidney-derived cell lines respectively, and find let-7a/b not only target cancer-related genes and lincRNAs, but also regulate lin-28 and Dicer1 expression to constitute incoherent feed-forward loop through the canonical seed matching mechanism. We also determine the non-canonical pairing for let-7b can bind to CDS region significantly down-regulate the target genes in human and macaque. Additionally, the non-canonical target sites in 5’-UTRs can repress translational efficiency of target genes of let-7b. By comparison of evolutionary analysis of 16 species 3’-UTRs, such as cross-species gaining miRNA target sites, we found the let-7 mediated the repression effect of ancient sites was much stronger than recent sites. Our results provide comprehensive and novel insights into the coding and non-coding gene regulation by let-7 family miRNAs in mammal evolution