Autoregulation\nof TRF2 through G‑Quadruplex-Specific\nInteraction between the Gene and N‑Terminal Domain of the Protein

Telomere repeat-binding factor 2 (TRF2) is a key component\nof the\nshelterin complex which guards the integrity of the telomere. Most\nof the TRF2 discussed previously was focused on the telomere, and\nrelatively less is discussed on aspects other than that. It is proved\nthat TRF2 also localizes to other potential G-quadruplex-forming sequences\namong the whole genome besides the telomere. Therefore, it may participate\nin regulating genes generally except for the well-known function of\nprotecting telomeres. Here, we demonstrate that the N-terminal basic\ndomain of TRF2 (TRF2B) can interact with the G-quadruplex formed by\nthe 5′-UTR sequence of its gene. Subsequently, this interaction\nwas identified as G-quadruplex-specific. Using a reporter gene system,\nwe proved that the translation of the reporter gene was dramatically\nreduced, triggered by the interaction between TRF2B and the G-quadruplex.\nAltogether, we propose that TRF2 can be “auto-regulated”\nthrough the G-quadruplex formed by its own gene sequence. This finding\nindicates a potential feedback mechanism in the regulation of the\nTRF2 gene. Additionally, it suggests a common mode in gene regulation\ninvolving the cooperation of TRF2 and the G-quadruplex.