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  • Qki activates Srebp2-mediated cholesterol biosynthesis for maintenance of eye lens transparency.

Qki activates Srebp2-mediated cholesterol biosynthesis for maintenance of eye lens transparency.

Nature communications (2021-05-23)
Seula Shin, Hao Zhou, Chenxi He, Yanjun Wei, Yunfei Wang, Takashi Shingu, Ailiang Zeng, Shaobo Wang, Xin Zhou, Hongtao Li, Qiang Zhang, Qinling Mo, Jiafu Long, Fei Lan, Yiwen Chen, Jian Hu
ABSTRACT

Defective cholesterol biosynthesis in eye lens cells is often associated with cataracts; however, how genes involved in cholesterol biosynthesis are regulated in lens cells remains unclear. Here, we show that Quaking (Qki) is required for the transcriptional activation of genes involved in cholesterol biosynthesis in the eye lens. At the transcriptome level, lens-specific Qki-deficient mice present downregulation of genes associated with the cholesterol biosynthesis pathway, resulting in a significant reduction of total cholesterol level in the eye lens. Mice with Qki depletion in lens epithelium display progressive accumulation of protein aggregates, eventually leading to cataracts. Notably, these defects are attenuated by topical sterol administration. Mechanistically, we demonstrate that Qki enhances cholesterol biosynthesis by recruiting Srebp2 and Pol II in the promoter regions of cholesterol biosynthesis genes. Supporting its function as a transcription co-activator, we show that Qki directly interacts with single-stranded DNA. In conclusion, we propose that Qki-Srebp2-mediated cholesterol biosynthesis is essential for maintaining the cholesterol level that protects lens from cataract development.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Pararosaniline Solution
Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-15, ascites fluid