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

Figure 4

Relief of miRNA-mediated CAT-1 repression according to cell response to radiation. High AMP/ADP in cell is accompanied by the cell exposure to radiation. Consequently, AMP-kinase activity is enhanced, which then leads to HuR (an RNA binding protein that interacts with ARE in 3′UTR of the mRNA) dephosphorylation, releasing from nucleus to cytoplasm and entering to processing bodies (PBs). In P bodies, HuR dissociates miRNP from CAT-1 mRNA and mobilizes it to stress granules (SGs). Within SGs, CAT-1 expression is elevated via recruiting polysomes and relieved from miR-122-mediated downregulation by HuR replacement of miRNP in PBs. Moreover, HuR binds to ARE sites of mRNAs in nucleus and chaperones them to the cytoplasm which then are relocalized in polysomes and contributes in delays onset of RNA decay by competing with AMD effectors.