Lei Ming’s team fromthe Institute of Precision Medicine reveals the molecular mechanisms of telomere-binding proteins affecting spermatogenesis

On October 30, TERB1-TRF1 interaction is crucial for male meiosisfrom Lei Ming‘s team was published as a long article onlinein Nature Structural & Molecular Biology, revealing the important molecular mechanism of the interaction between telomere-binding protein TRF1and TERB1 during spermatogenesis.

Telomeres are located at the ends of linear eukaryotes and consist of DNA repeats and telomere-binding proteins. In the pre-meiotic stage, telomeres will adhere to the nuclear membrane and accumulate together to form a bouquet, which is very conserved during meiosis and is believed to be importantin correcting pairing and segregation of homologous chromosomes. In mammals, the pre-meiotic special expression of proteinTERB1 leads to telomere forming a bouquet through binding protein TRF1. However, it is still unclear about the specific regulation mechanism of TERB1 and its physiological significance.

In this study, Lei’s team successfully resolved the crystal structure of the TERB1-TRF1 complex, based on which they constructed a mouse model that specifically disrupted the TERB1-TRF1 interaction, and thus found the special molecular mechanismthat telomeres help XY chromosome pair during meiosis. In the mouse model of Terb1 mutation, the localization of TERB1 on telomeres was significantly reduced, affecting the efficiency of telomere aggregation and mutual recognition of homologous chromosomes in spermatocytes, which blockedthe process of spermatocytes entering from thezygotene phase to thepachynema stage. Autosomes or XX chromosomes can rely on the entire chromosome to pair and associate, while XY pairing can only rely on a short pseudo-homologous region (PAR) near its telomere on its short arm, as a result,there are a large number of unmatched X and Y chromosomes in spermatocytes escaped into pachynema stage, whose abnormality causes obvious apoptotic signals and vacuolar structures in the seminiferous tubules that cannot produce large amounts of haploid cells continuously and ultimately affect the male fertility.

The Institute of Precision Medicine, as one of Shanghai University IV-class peak subjects, is led by the Shanghai JiaoTong University School of Medicine(SJTU-SM) and affiliated to the Ninth People‘s Hospital for the entity of construction. As a research institute of SJTU-SM, the Institute of Precision Medicine aims at the research of chronic diseases that significantly threaten human health, such as cancer, metabolic diseases, neurodegenerative diseases and cardiovascular diseases, and based ona great number of dataof individual genetic background, environmental factors and lifestyle, make key breakthrough to achieve precise prevention, diagnosis and treatment.