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. 2023 Dec;39(6):2881-2898.
doi: 10.1007/s10565-023-09807-8. Epub 2023 Apr 25.

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

Jin Yang  1   2   3 , Xiaobai Liu  1   2   3 , Yubo Zhao  1   2   3 , Weiwei Dong  1   2   3 , Yixue Xue  4 , Xuelei Ruan  4 , Ping Wang  4 , Libo Liu  4 , Tiange E  1   2   3 , Jian Song  1   2   3 , Zheng Cui  1   2   3 , Yunhui Liu  5   6   7
Affiliations

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

Jin Yang et al. Cell Biol Toxicol. 2023 Dec.

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.

Keywords: Apoptosis; Chronic cerebral ischemia; Pseudouridylation; RNCR3; Snora62.

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