Translational regulation of PGHS-1 mRNA: 5′ untranslated region and first two exons conferring negative regulation

RNA-binding protein nucleolin in disease

“…Binding of nucleolin to the 5' UTR nucleolin response element (NRE) of the prostaglandin endoperoxide H synthase-1 (PGHS1) mRNA reduced translation of the encoded proinflammatory enzyme Pghs-1 in megakaryoblastic cells. 50 Interestingly, NF45 and NF90 also associated with the 5' UTR of PGHS1 mRNA and repressed its translation, 51 although the possible functional links among these RBPs to control Pghs1 production have not been reported.…”

Characterization of proteins associating with 5’ terminus of PGHS-1 mRNA

“…Induction of PGHS-1 gene expression is not limited to hematopoietic cells but also has been documented in neuroblastoma cell lines and in human nasal mucosa cells, emphasizing the importance of regulation at the translational step for PGHS-1 gene expression [12,13]. Previous work from our laboratory has shown that the 5'UTR and the first two exons of PGHS-1 mRNA had a large impact on decreasing the translational efficiency of a reporter gene [14]. The 5'UTR and first two exons sequence must be present in order to have a negative effect on translation and suggest the presence of a secondary structure required for this activity.…”

“…The 5'UTR and first two exons sequence must be present in order to have a negative effect on translation and suggest the presence of a secondary structure required for this activity. This 5'end of PGHS-1 mRNA sequence has also been shown to directly interact with nucleolin protein [14]. Additional experiments have shown that mutation of the two nucleolin response elements (NRE) [15] found within PGHS-1 5'UTR and the first two exons, respectively, partially reduced the negative effects when reporter constructs were tested [14].…”

“…This 5'end of PGHS-1 mRNA sequence has also been shown to directly interact with nucleolin protein [14]. Additional experiments have shown that mutation of the two nucleolin response elements (NRE) [15] found within PGHS-1 5'UTR and the first two exons, respectively, partially reduced the negative effects when reporter constructs were tested [14]. Once exported to the cytoplasm, not all mRNAs immediately enter the translationally active pool, some are held in a translationally silent state awaiting either proper subcellular localization or a signal that the appropriate protein synthesis is now required [16].…”

Modulation of Gene Expression by RNA Binding Proteins: mRNA Stability and Translation

“…However, nucleolin binds the 3'UTR of APP mRNA, promoting its decay [78][79][80][81][82][83]. While nucleolin enhances the translation of mRNAs encoding for matrix metallopeptidase 9 (MMP9), AKT1 and cyclin I (CCNI) through binding to the 3'UTR, it suppresses translation of genes encoding for the tumor protein p53 (TP53) and prostaglandin endoperoxide H synthase-1 (PGHS-1) through binding to the 5'UTR [3,84,85].…”