Position and stability are determining factors for translation repression by an RNA G-quadruplex-forming sequence within the 5' UTR of the NRAS proto-oncogene.
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.
Kumari
Sunita
S
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
Bugaut
Anthony
A
Balasubramanian
Shankar
S
D020121:5' Untranslated Regions / Q000235:genetics*; D001483:Base Sequence; D002474:Cell-Free System; D054856:G-Quadruplexes; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D009154:Mutation; D009691:Nucleic Acid Denaturation; D014176:Protein Biosynthesis / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics; D013816:Thermodynamics; D044366:Transition Temperature
D020121:5' Untranslated Regions; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D012313:RNA; D016283:Proto-Oncogene Proteins p21(ras)