Wash-free super-resolution sensing of telomeric G-quadruplex/t-loop states in living cells using a cyclometalated Ir(III) probe.

Xiaojuan Xu, Liping Su, Lin Bai, Ruicen Li, Kaifeng Wu, Xiaohe Tian, Liulin Xiong

Department of Anesthesiology, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, Guizhou Province, 563000, P. R. China; Department of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology and Medical Imaging, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610041, P. R. China; School of Biology and Food Engineering, Hefei Normal University, Hefei, Anhui Province, 230031, P. R. China; High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui Province, 230031, P. R. China.Department of Anesthesiology, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, Guizhou Province, 563000, P. R. China; Department of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology and Medical Imaging, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610041, P. R. China; School of Biology and Food Engineering, Hefei Normal University, Hefei, Anhui Province, 230031, P. R. China; High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui Province, 230031, P. R. China. · pubmed

Paper

Abstract

We present a fluorogenic cyclometalated Ir(III) probe (cIr-Q) that selectively lights up telomeric G-quadruplexes (GQs), features a large Stokes shift (∼168 nm), high photostability, rapid passive nuclear entry (≤2 min), and wash-free operation. Integrated with super-resolution microscopy, cIr-Q enables in situ quantification of higher-order telomeric architectures in living cells. NMR and biochemical assays further delineate a TERRA-initiated pathway: RNA-DNA hybridization exposes the G-rich strand to fold into GQs that facilitate t-loop formation. In a senescence model, cIr-Q reports an aging-associated decrease of GQs/t-loop signals. These results establish cIr-Q as a practical biosensing platform for live-cell readout of telomeric structural biomarkers, bridging materials design with chromosome biology without fixation or permeabilization.

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Research summary

The development of a wash-free, super-resolution probe for telomeric G-quadruplexes enables more accurate live-cell imaging of telomere structural dynamics, which are fundamental mechanisms in cellular aging and genomic stability. This tool facilitates better understanding of telomere maintenance, a key hallmark of aging, by allowing non-invasive observation of t-loop formation and G-quadruplex states without fixation artifacts.

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