Mechanisms of miRNA-Mediated Gene Regulation from Common Downregulation to mRNA-Specific Upregulation

Figure 1

Potential mechanisms of miRNA-mediated downregulation. Ribonucleoproteins (miRNPs) target mRNAs through sequence complementation. The association between miRNPs and mRNAs can have one or several consequences. miRNP-mediated downregulation may have direct and indirect mechanisms and occur before translation is triggered or after translation initiation. (a–c) Translation initiation mechanisms. miRNP interferes with early steps of translation before elongation. (a) miRNPs recruit several factors and enzymes for mRNA cleavage and degradation including decapping enzymes, deadenylase, 3′ and 5′ exonucleases, and endonucleases. (b, c) Argonaute protein competes with cap binding proteins (CBPs) and elf4E for binding to cap structure and inhibits translation initiation by interfering with mRNA circularization and formation of closed-loop achieved through cap structure interaction with CBPs and elf4E/G required for translation initiation. (d–h) Postinitiation mechanisms. miRNPs repress translation elongation and termination or involve in protein degradation and sequestration. (d, e) miRNP interferes with ribosome subunit by inhibiting its joining or promoting its dissociation. (f, g) miRNP obstructs translation elongation by competing with elongation factors or cotranslationally recruiting protein decay factors such as exosomes. (h) Target mRNA is sequestered from translation machinery and stored or sometimes is degraded by enzymes. However, alternatively, translationally inhibited mRNA along with associated proteins could be sequestered at the same bodies. For explanations in support of illustrations, refer to the main text.