The Role of miR-378a in Metabolism, Angiogenesis, and Muscle Biology

Figure 1

miRNA biogenesis. miRNAs are transcribed as mRNA transcripts from the genome by polymerase II as pre-miRs. Endoribonuclease drosha and DGCR8 excise pre-miRs from the primary transcripts. Pri-miRs are exported from the nucleus by exportin-5. An endoribonuclease dicer processes the pre-miRNA and removes the hair loop sequence, creating a double stranded miRNA duplex. One or both strands can be incorporated in RNA-induced silencing complex RISC, which allows the miRNA to suppress translation of their target mRNA or cleave the mRNA and lead to the degradation of it. miRNA-induced RISC can act on their targets by three ways. When there is perfect pairing between the miRNA sequence and its target site, the mRNA is cleaved (A). If the pairing is partial, deadenylation of the mRNA via recruitment of the CCR4-NOT complex takes place and the poly-A tail is lost, leaving the mRNA vulnerable to RNAse activity and mRNA degradation (B). As a second manner of action when pairing is not perfect, the miRNA-induced RISC can also induce repression of translation by blocking initiation or further steps of translation, by mechanisms such as, for example, the promotion of ribosome drop-off from the mRNA transcript or destabilization of the mRNA cap binding protein (C).