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

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.

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Acknowledgements

We thank Professor Jinpeng Sun in Qilu Medical College of Shandong University for helpful discussions. This work was supported by a grant from the National Natural Science Foundation of China (NSFC) (No. 81322014) to XS and the Canadian Institutes of Health Research (CIHR) Operating Grant MOP-142487 to WS. WS was the holder of the Tier 1 Canada Research Chair in Alzheimer’s disease.

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XS and WS conceived and designed the experiments; YY and CZ performed the experiments; YY, YZ, PW, LH, ST, CV-G, WS and XS analyzed and contributed reagents/materials/analysis tools; XS, YZ and WS wrote the paper. All authors reviewed the manuscript.

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Correspondence to Weihong Song or Xiulian Sun.

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Yun, Y., Zhang, Y., Zhang, C. et al. Regulator of calcineurin 1 is a novel RNA-binding protein to regulate neuronal apoptosis. Mol Psychiatry 26, 1361–1375 (2021). https://doi.org/10.1038/s41380-019-0487-0

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