Human Telomeric i-motif: Its Structure‚ Recognition and Physiological Activity
10.13865/j.cnki.cjbmb.2023.05.1606
- Author:
Xiao-Jie CUI
1
;
Jun-Liu HUANG
2
;
Yun ZHANG
2
;
Xiao-Jie CUI
2
Author Information
1. Key Laboratory of Ecology and Environment in Minority areas, Minzu University of China
2. Department of Chemistry and Environmental Sciences, College of Life and Environmental Sciences, Minzu University of China
- Publication Type:Journal Article
- Keywords:
cancer treatment;
human telomeres;
intercalated motif(i-motif / iM);
ligand recognition;
structures
- From:
Chinese Journal of Biochemistry and Molecular Biology
2023;39(11):1524-1533
- CountryChina
- Language:Chinese
-
Abstract:
The human telomeric i-motif (htel-iM) is a unique higher-order DNA structure formed by the cytosine-rich (C) sequences at the end of human telomeres. Studies have shown that htel-iM plays a significant role in the transcriptional regulation of telomeric repeat-containing RNA (TERRA) ‚ maintenance of telomere function and inhibition of telomerase activity. Thus‚ it is closely related to the development and progression of many cancers and is a promising new target for cancer treatment therapy. Compared to other nucleic acid higher-order structures such as G-quadruplexes‚ the stability of htel-iM is much weaker and affected by many factors like buffer pH‚ ionic conditions and molecular crowding environments. Therefore the existence of the iM structures in near neutral physiological conditions has been uncertain for a long time. Recently‚ using in-vitro screened small molecule ligands to selectively recognize and stabilize htel-iM provides a new strategy for the exploration of the biological relevance of htel-iM. Thus it has become a research hotspot to take telomere as a cancer treatment target. However‚ so far the reported small molecule ligands selectively targeting the htel-iM are far from sufficient compared with those targeting other higher-order nucleic acid structures. In this review‚ the discovery and the characteristic of the iM structures are briefly described‚ with an emphasis on the in-vitro affecting factors of the htel-iM structure‚ the reported htel-iM ligands and its biological relevance and regulation mechanisms‚ which will be helpful in further exploration of the htel-iM structure and ligand screening in near physiological conditions‚ and understanding the mechanism and developing novel therapeutic strategies for cancer treatment targeting the htel-iM structures.
