02321nas a2200181   4500008004100000022001400041245010600055210006900161260007100230300001400301490000700315520160500322100002101927700002501948700001701973700001801990856013102008       2013                        eng d  a0006-296000aG-quadruplex augments translation in the 5 ` untranslated region of transforming growth factor beta 20 aGquadruplex augments translation in the 5 untranslated region of  a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcMAR  a1528-15380 v523 a<p>Transforming growth factor beta 2 (TGF beta 2) is a versatile cytokine with a prominent role in cell migration, invasion, cellular development, and immunomodulation. TGF beta 2 promotes the malignancy of tumors by inducing epithelial-mesenchymal transition, angiogenesis, and immunosuppression. As it is well-documented that nucleic acid secondary structure can regulate gene expression, we assessed whether any secondary motif regulates its expression at the post-transcriptional level. Bioinformatics analysis predicts an existence of a 23-nucleotide putative G-quadruplex sequence (PG4) in the 5' untranslated region (UTR) of TGF beta 2 mRNA. The ability of this stretch of sequence to form a highly stable, intramolecular parallel quadruplex was demonstrated using ultraviolet and circular dichroism spectroscopy. Footprinting studies further validated its existence in the presence of a neighboring nucleotide sequence. Following structural characterization, we evaluated the biological relevance of this secondary motif using a dual luciferase assay. Although PG4 inhibits the expression of the reporter gene, its presence in the context of the entire 5' UTR sequence interestingly enhances gene expression. Mutation or removal of the G-quadruplex sequence from the 5' UTR of the gene diminished the level of expression of this gene at the translational level. Thus, here we highlight an activating role of the G-quadruplex in modulating gene expression of TGF beta 2 at the translational level and its potential to be used as a target for the development of therapeutics against cancer.</p>1 aAgarwala, Prachi1 aPandey, Satyaprakash1 aMapa, Koyeli1 aMaiti, Souvik  uhttps://library.ncl.res.in/content/g-quadruplex-augments-translation-5-untranslated-region-transforming-growth-factor-beta-2-0