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Figure 1 | Molecular and Cellular Therapies

Figure 1

From: Therapeutic opportunities for targeting microRNAs in cancer

Figure 1

miRNA biogenesis. miRNAs are transcribed by RNA polymerase II or III (Pol II/III) to produce primary transcripts (pri-miRNAs), which are subsequently processed and cropped via the actions of the Drosha-DGCR8 complex, which together with the RNA helicases p68 and p72 generate the formation of precursor miRNAs (pre-miRNAs). Activation of the TGF-β, Akt/PI3K, and p53 signaling systems have all been shown to promote the processing of specific pri-miRNAs, while stimulation of the ER-α signaling system is capable of repressing pri-miRNA processing. Once processed, pre-miRNAs hairpins are exported from the nucleus by exportin-5 (XPO5)-RanGTPase complexes, and are subsequently cleaved by Dicer:TRBP complexes, thereby producing mature oligonucleotide duplexes. The rate at which Dicer cleaves pre-miRNAs is greatly enhanced by the phosphorylation of TRBP by Erk1/2. At the completion of pre-miRNA cleavage, Dicer serves with Argonaute (Ago) 2 in loading mature miRNAs into RNA-induced silencing complexes (RISCs), thereby silencing target mRNA expression through mRNA cleavage, translational repression, or deadenylation. Hypoxic conditions resulting in EGFR activation have been shown to induce the phosphorylation of Ago2, leading to diminished maturation reactions of select miRNAs.

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