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. Author manuscript; available in PMC: 2018 Aug 1.
Published in final edited form as: Arch Toxicol. 2017 May 13;91(8):2781–2797. doi: 10.1007/s00204-017-1974-1

Figure 1. MiRNA expression, processing and function are highly organized.

Figure 1

MicroRNA biogenesis begins with transcription of genomic DNA by RNA polymerase II and can be mediated by many common transcription factors. Often, large RNA stem-loop structures called pri-miRNAs are formed directly. Drosha then cleaves pri-miRNAs to form intermediate stem-loop structures called pre-miRNAs. Alternatively, pre-miRNAs can form through an intermediate called a “miRtron” from splicing of mRNA. Exportin 5 (XPO5) then transports pre-miRNAs through nuclear pore complexes (NPC) into the cytosol. In the cytosol, Dicer cleaves pre-miRNAs to form microRNA duplexes. Argonaute 2 (AGO2) then mediates the dissociation of the miRNA duplex to form two mature miRNAs. These two miRNAs are deemed “5p” or “3p” depending on whether they originate from the 5′ or 3′ end of the pre-miRNA, respectively. Depending on the context or specific miRNA, mature miRNAs will either assemble within RNA-induced silencing complexes (RISC), degrade or may reenter the nucleus via Importin 8 (IPO8) to regulate transcription. After RISC assembly, miRNAs can bind to mRNAs with their complementary seed region to the 3′ untranslated region (UTR), 5′ UTR or the open reading frame (ORF). MiRNAs then regulate protein production either by promoting mRNA degradation or by inhibiting translation.