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Mechanism of Dcp2/RNCR3/Dkc1/Snora62 axis regulating neuronal apoptosis in chronic cerebral ischemia

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Abstract  

RNA-binding proteins (RBPs), long non-coding RNAs (lncRNAs), and small nucleolar RNAs (snoRNAs) were found to play crucial regulatory roles in ischemic injury. Based on GEO databases and our experimental results, we selected Dcp2, lncRNA-RNCR3, Dkc1, and Snora62 and Foxh1 as research candidates. We found that expression levels of Dcp2, RNCR3, Dkc1, Snora62, and Foxh1 were upregulated in oxygen glucose deprivation-treated HT22 cells and hippocampal tissues subject to chronic cerebral ischemia (CCI). Silencing of Dcp2, RNCR3, Dkc1, Snora62, and Foxh1 all inhibited apoptosis of oxygen glucose deprivation-treated HT22 cells. Moreover, Dcp2 promoted RNCR3 expression by increasing its stability. Importantly, RNCR3 may act as a molecular skeleton to bind to Dkc1 and recruit Dck1 to promote snoRNP assembly. Snora62 was responsible for pseudouridylation at 28S rRNA U3507 and U3509 sites. Pseudouridylation levels of 28S rRNA were reduced after knockdown of Snora62. Decreased pseudouridylation levels inhibited the translational activity of its downstream target, Foxh1. Our study further confirmed that Foxh1 transcriptionally promoted the expression of Bax and Fam162a. Notably, experiments in vivo showed that Dcp2 knockdown combined with RNCR3 knockdown and Snora62 knockdown resulted in an anti-apoptosis effect. In conclusion, this study suggests that the axis Dcp2/RNCR3/Dkc1/Snora621 is important for the regulation of neuronal apoptosis induced by CCI.

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Data availability

The data used that support the findings of this study are available from the corresponding author on reasonable request.

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Funding

This work is supported by grants from the Natural Science Foundation of China (82173071), China Postdoctoral Science Foundation (2022M723519), and Outstanding Scientific Fund of Shengjing Hospital (201802).

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Authors and Affiliations

  1. Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China

    Jin Yang, Xiaobai Liu, Yubo Zhao, Weiwei Dong, Tiange E, Jian Song, Zheng Cui & Yunhui Liu

  2. Key Laboratory of Neuro-Oncology in Liaoning Province, Shenyang, 110004, China

    Jin Yang, Xiaobai Liu, Yubo Zhao, Weiwei Dong, Tiange E, Jian Song, Zheng Cui & Yunhui Liu

  3. Liaoning Medical Surgery and Rehabilitation Robot Technology Engineering Research Center, Shenyang, 110004, China

    Jin Yang, Xiaobai Liu, Yubo Zhao, Weiwei Dong, Tiange E, Jian Song, Zheng Cui & Yunhui Liu

  4. Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, China

    Yixue Xue, Xuelei Ruan, Ping Wang & Libo Liu

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  1. Jin Yang
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  2. Xiaobai Liu
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  3. Yubo Zhao
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  9. Tiange E
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  10. Jian Song
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Contributions

JY was mainly responsible for experiments and data collecting. YBZ, WWD, and XBL mainly contributed to data analysis. JY, XLR, TGE, JS, and ZC mainly contributed to materials preparing and submission. YXX, LBL, and PW were mainly responsible for proofreading. YHL designed the research. All authors approved the final paper.

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Correspondence to Yunhui Liu.

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For the animal studies, a protocol detailing experimental procedures following the China Medical University guidelines was submitted to and approved by Ethics Committee of China Medical University.

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Yang, J., Liu, X., Zhao, Y. et al. Mechanism of Dcp2/RNCR3/Dkc1/Snora62 axis regulating neuronal apoptosis in chronic cerebral ischemia. Cell Biol Toxicol 39, 2881–2898 (2023). https://doi.org/10.1007/s10565-023-09807-8

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