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J Am Chem Soc. 2010 Dec 22;132(50):17831-9. doi: 10.1021/ja106287x. Epub 2010 Nov 24.

An RNA G-quadruplex is essential for cap-independent translation initiation in human VEGF IRES.

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Department of Chemistry and Biochemistry, Kent State University, Kent, Ohio 44242, United States.


RNA G-quadruplexes located within the 5'-UTR of mRNA are almost always known to be associated with repression of cap-dependent translation. However, in this report we present functional as well as structural evidence that sequence redundancy in a G-rich segment within the 5'-UTR of human VEGF mRNA supports a 'switchable' RNA G-quadruplex structure that is essential for IRES-mediated translation initiation. Additionally, utilization of a specific combination of G-tracts within this segment allows for the conformational switch that implies a tunable regulatory role of the quadruplex structure in translation initiation. A sequence engineered from a functionally handicapped mutant moderately rescued the activity, further indicating the importance of G-quadruplex structure for VEGF IRES-A function. This to our knowledge is the first report of a conformationally flexible RNA G-quadruplex which is essential for IRES-mediated translation initiation.

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