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钙调神经磷酸酶1调节因子是一种新型的RNA结合蛋白,可调节神经元凋亡。

Regulator of calcineurin 1 is a novel RNA-binding protein to regulate neuronal apoptosis.

作者信息

Yun Yan, Zhang Yun, Zhang Chen, Huang Liyan, Tan Shichuan, Wang Pin, Vilariño-Gúell Carles, Song Weihong, Sun Xiulian

机构信息

Department of Neurology, Qilu Hospital of Shandong University, No. 107 West Wenhua Road, 250012, Jinan, Shandong Province, China.

Brain Research Institute, Qilu Hospital of Shandong University, No.107 West Wenhua Road, 250012, Jinan, Shandong Province, China.

出版信息

Mol Psychiatry. 2021 Apr;26(4):1361-1375. doi: 10.1038/s41380-019-0487-0. Epub 2019 Aug 27.

Abstract

Posttranscriptional regulation of gene expression plays an important role in the maturation, transport, stability and translation of coding and noncoding RNAs. RNA-binding protein (RBP) is a key factor of the regulation. Regulator of calcineurin 1 (RCAN1) is a multifunctional protein involved in neurodegeneration, mitochondrial dysfunction, inflammation and protein glycosylation, and plays an important role in the pathogenesis of Down syndrome and Alzheimer's disease. In this report, we discovered that RCNA1 is a novel RNA-binding protein. A 23 nucleotide sequence of adenine nucleotide translocator (ANT1) mRNA was identified as the binding motif of RCAN1. Furthermore, we found that R1SR13, as the RNA aptamer of RCAN1 identified by SELEX, blocked RCAN1-induced inhibition of the nuclear factor of activated T cells (NFAT) and NF-κB signaling pathways, and reduced neuronal apoptosis. Taken together, our results demonstrate that RCAN1 is a novel RNA-binding protein and the RNA aptamer of RCAN1 plays a neuroprotective role.

摘要

基因表达的转录后调控在编码和非编码RNA的成熟、转运、稳定性及翻译过程中发挥着重要作用。RNA结合蛋白(RBP)是该调控的关键因素。钙调神经磷酸酶1调节因子(RCAN1)是一种多功能蛋白,参与神经退行性变、线粒体功能障碍、炎症及蛋白质糖基化过程,在唐氏综合征和阿尔茨海默病的发病机制中起重要作用。在本报告中,我们发现RCNA1是一种新型RNA结合蛋白。腺嘌呤核苷酸转运体(ANT1)mRNA的一段23个核苷酸序列被确定为RCAN1的结合基序。此外,我们发现,作为通过指数富集的配体系统进化(SELEX)鉴定出的RCAN1的RNA适配体,R1SR13可阻断RCAN1诱导的活化T细胞核因子(NFAT)和核因子κB(NF-κB)信号通路的抑制,并减少神经元凋亡。综上所述,我们的结果表明RCAN1是一种新型RNA结合蛋白,且RCAN1的RNA适配体具有神经保护作用。

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