Autoregulation of TRF2 through G-Quadruplex-Specific Interaction between the Gene and N-Terminal Domain of the...

Telomere repeat-binding factor 2 (TRF2) is a key component of the shelterin complex which guards the integrity of the telomere. Most of the TRF2 discussed previously was focused on the telomere, and relatively less is discussed on aspects other than that. It is proved that TRF2 also localizes to other potential G-quadruplex-forming sequences among the whole genome besides the telomere. Therefore, it may participate in regulating genes generally except for the well-known function of protecting telomeres. Here, we demonstrate that the N-terminal basic domain of TRF2 (TRF2B) can interact with the G-quadruplex formed by the 5'-UTR sequence of its gene. Subsequently, this interaction was identified as G-quadruplex-specific. Using a reporter gene system, we proved that the translation of the reporter gene was dramatically reduced, triggered by the interaction between TRF2B and the G-quadruplex. Altogether, we propose that TRF2 can be "auto-regulated" through the G-quadruplex formed by its own gene sequence. This finding indicates a potential feedback mechanism in the regulation of the TRF2 gene. Additionally, it suggests a common mode in gene regulation involving the cooperation of TRF2 and the G-quadruplex.