Fig. 3

The regulatory mechanism of LIN-28A&B on the biogenesis of Let-7 miRNA. Let-7 miRNA is transcribed by RNA pol. II. The initial transcript called primary microRNA (pri-miRNA) that contains an imperfectly double-stranded region within a hairpin loop, in addition to 5′ and 3′ ends, then it is cleaved by DROSHA, which removes the 5′ and 3′ ends and produces a short hairpin called the pre-miRNA in the nucleus. After that, pre-miRNA is transferred through Exportin-5 to the cytoplasm where it is bound by the RISC that contains DICER, which cleaves the pre-miRNA and produces Let-7 dsRNA, which will be bound by the RISC that contains DICER and cleaved to two separate stands, one of them, the passenger strand will be removed while the guide strand will be retained. LIN28B inhibits the formation of mature Let-7 by inhibiting DROSHA, while LIN28A inhibits DICER in the cytoplasm and promotes the uridynylation of pre-Let-7 thus preventing the formation of mature Let-7