Journal
BIOCHEMISTRY
Volume 47, Issue 48, Pages 12664-12669Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bi8010797
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Funding
- BBSRC
- Cancer Research UK
- Cambridge Commonwealth Trust
- Trinity College, Cambridge
- BBSRC [BB/E019773/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/E019773/1] Funding Source: researchfish
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Nucleic acid secondary structures in the 5' untranslated regions (UTRs) of mRNAs have been shown to play a critical role in translation regulation. We recently demonstrated that a naturally occurring, conserved, and stable RNA G-quadruplex element (5'-GGGAGGGGCGGGUCUGGG-3'), located close to the 5' cap within the 5' UTR of the NRAS proto-oncogene mRNA, modulates gene expression at the translational level. Herein, we show that the translational effect of this G-quadruplex motif in NRAS 5' UTR is not uniform, but rather depends on the location of the G-quadruplex-forming sequence. The RNA G-quadruplex-forming sequence represses translation when situated relatively proximal to the 5' end., within the first 50 nt, in the 5' UTR of the NRAS proto-oncogene, whereas it has no significant effect on translation if located comparatively away from the 5' end. We have also demonstrated that the thermodynamic stability of the RNA G-quadruplex at its natural position within the NRAS 5' UTR is an important factor contributing toward its ability to repress translation.
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