Long noncoding RNA BS-DRL1 modulates the DNA damage response and genome stability by interacting with HMGB1 in neurons

Min-Min Lou, Xiao-Qiang Tang, Guang-Ming Wang, Jia He, Fang Luo, Ming-Feng Guan, Fei Wang, Huan Zou, Jun-Ying Wang, Qun Zhang, Ming-Jian Xu, Qi-Li Shi, Li-Bing Shen, Guo-Ming Ma, Yi Wu, Yao-Yang Zhang, Ai-bin Liang, Ting-Hua Wang, Liu-Lin Xiong, Jian Wang (), Jun Xu () and Wen-Yuan Wang ()
Additional contact information
Min-Min Lou: Chinese academy of Science
Xiao-Qiang Tang: Chinese academy of Science
Guang-Ming Wang: Tongji University School of Medicine
Jia He: Chinese academy of Science
Fang Luo: Chinese academy of Science
Ming-Feng Guan: Chinese academy of Science
Fei Wang: Chinese academy of Science
Huan Zou: Chinese academy of Science
Jun-Ying Wang: Chinese academy of Science
Qun Zhang: Huashan Hospital, Fudan University
Ming-Jian Xu: Chinese academy of Science
Qi-Li Shi: Chinese academy of Science
Li-Bing Shen: Chinese academy of Science
Guo-Ming Ma: Chinese academy of Science
Yi Wu: Huashan Hospital, Fudan University
Yao-Yang Zhang: Chinese academy of Science
Ai-bin Liang: Tongji University School of Medicine
Ting-Hua Wang: Kunming medical University
Liu-Lin Xiong: Kunming medical University
Jian Wang: Huashan Hospital, Fudan University
Jun Xu: Tongji University School of Medicine
Wen-Yuan Wang: Chinese academy of Science

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract Long noncoding RNAs (lncRNAs) are known to regulate DNA damage response (DDR) and genome stability in proliferative cells. However, it remains unknown whether lncRNAs are involved in these vital biological processes in post-mitotic neurons. Here, we report and characterize a lncRNA, termed Brain Specific DNA-damage Related lncRNA1 (BS-DRL1), in the central nervous system. BS-DRL1 is a brain-specific lncRNA and depletion of BS-DRL1 in neurons leads to impaired DDR upon etoposide treatment in vitro. Mechanistically, BS-DRL1 interacts with HMGB1, a chromatin protein that is important for genome stability, and is essential for the assembly of HMGB1 on chromatin. BS-DRL1 mediated DDR exhibits cell-type specificity in the cortex and cerebellum in gamma-irradiated mice and BS-DRL1 knockout mice show impaired motor function and concomitant purkinje cell degeneration. Our study extends the understanding of lncRNAs in DDR and genome stability and implies a protective role of lncRNA against neurodegeneration.

Date: 2021
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DOI: 10.1038/s41467-021-24236-z

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