A G-quadruplex structure within the 5′-UTR of TRF2 mRNA represses translation in human cells
نویسندگان
چکیده
Telomeres protect chromosome ends from being recognized as double-stranded breaks. Telomeric function is ensured by the shelterin complex in which TRF2 protein is an essential player. The G-rich strand of telomere DNA can fold into G-quadruplex (G4) structure. Small molecules stabilizing G4 structures, named G4 ligands, have been shown to alter telomeric functions in human cells. In this study, we show that a guanine-rich RNA sequence located in the 5'-UTR region of the TRF2 mRNA (hereafter 91TRF2G) is capable of forming a stable quadruplex that causes a 2.8-fold decrease in the translation of a reporter gene in human cells, as compared to a mutant 5'-UTR unable to fold into G4. We also demonstrate that several highly selective G4 ligands, the pyridine dicarboxamide derivative 360A and bisquinolinium compounds Phen-DC(3) and Phen-DC(6), are able to bind the 91TRF2G:RNA sequence and to modulate TRF2 protein translation in vitro. Since the naturally occurring 5'-UTR TRF2:RNA G4 element was used here, which is conserved in several vertebrate orthologs, the present data substantiate a potential translational mechanism mediated by a G4 RNA motif for the downregulation of TRF2 expression.
منابع مشابه
Inhibition of translation in living eukaryotic cells by an RNA G-quadruplex motif.
Guanine-rich sequences can adopt intramolecular four-stranded structures, called G-quadruplexes. These motifs have been intensively investigated on the DNA level, but their overall biological relevance remains elusive. Only recently has research concerning the function of G-quadruplexes in RNAs commenced. Here, we demonstrate for the first time, that an RNA G-quadruplex structure inhibits trans...
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