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

被引:25
作者
Yun, Yan [1 ,2 ]
Zhang, Yun [3 ]
Zhang, Chen [2 ,4 ]
Huang, Liyan [1 ,2 ]
Tan, Shichuan [1 ,2 ]
Wang, Pin [5 ]
Vilarino-Guell, Carles [6 ]
Song, Weihong [3 ]
Sun, Xiulian [2 ,7 ]
机构
[1] Shandong Univ, Dept Neurol, Qilu Hosp, 107 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China
[2] Shandong Univ, Brain Res Inst, Qilu Hosp, 107 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China
[3] Univ British Columbia, Townsend Family Labs, Dept Psychiat, Vancouver, BC V6T 1Z3, Canada
[4] Shandong Univ, Dept Pediat, Qilu Hosp, 107 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China
[5] Shandong Univ, Otolarygol Key Lab Natl Hlth Comm, Qilu Hosp, 107 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China
[6] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada
[7] Shandong Univ, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Minist Educ, Chinese Natl Hlth Commiss,Qilu Hosp, 107 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China
基金
中国国家自然科学基金; 加拿大健康研究院;
关键词
GENE-TRANSCRIPTION; RCAN1; OVEREXPRESSION; DSCR1; IDENTIFICATION; EXPRESSION; SELECTION; MCIP1;
D O I
10.1038/s41380-019-0487-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-kappa B 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.
引用
收藏
页码:1361 / 1375
页数:15
相关论文
共 45 条
[1]   Blood-derived amyloid-β protein induces Alzheimer's disease pathologies [J].
Bu, X-L ;
Xiang, Y. ;
Jin, W-S ;
Wang, J. ;
Shen, L-L ;
Huang, Z-L ;
Zhang, K. ;
Liu, Y-H ;
Zeng, F. ;
Liu, J-H ;
Sun, H-L ;
Zhuang, Z-Q ;
Chen, S-H ;
Yao, X-Q ;
Giunta, B. ;
Shan, Y-C ;
Tan, J. ;
Chen, X-W ;
Dong, Z-F ;
Zhou, H-D ;
Zhou, X-F ;
Song, W. ;
Wang, Y-J .
MOLECULAR PSYCHIATRY, 2018, 23 (09) :1948-1956
[2]   Cooperativity in RNA-Protein Interactions: Global Analysis of RNA Binding Specificity [J].
Campbell, Zachary T. ;
Bhimsaria, Devesh ;
Valley, Cary T. ;
Rodriguez-Martinez, Jose A. ;
Menichelli, Elena ;
Williamson, James R. ;
Ansari, Aseem Z. ;
Wickens, Marvin .
CELL REPORTS, 2012, 1 (05) :570-581
[3]   Identification of a peptide fragment of DSCR1 that competitively inhibits calcineurin activity in vitro and in vivo [J].
Chan, B ;
Greenan, G ;
McKeon, F ;
Ellenberger, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (37) :13075-13080
[4]   RNA recognition motifs:: boring?: Not quite [J].
Clery, Antoine ;
Blatter, Markus ;
Allain, Frederic H-T .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 2008, 18 (03) :290-298
[5]   Messenger-RNA-binding proteins and the messages they carry [J].
Dreyfuss, G ;
Kim, VN ;
Kataoka, N .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2002, 3 (03) :195-205
[6]   Chronic overexpression of the calcineurin inhibitory gene DSCR1 (Adapt78) is associated with Alzheimer's disease [J].
Ermak, G ;
Morgan, TE ;
Davies, KJA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (42) :38787-38794
[7]   RCAN1 in the inverse association between Alzheimer's disease and cancer [J].
Fu, Qiang ;
Wu, Yili .
ONCOTARGET, 2018, 9 (01) :54-66
[8]   Genomic organization, alternative splicing, and expression patterns of the DSCR1 (Down syndrome candidate region 1) gene [J].
Fuentes, JJ ;
Pritchard, MA ;
Estivill, X .
GENOMICS, 1997, 44 (03) :358-361
[9]   From Cis-Regulatory Elements to Complex RNPs and Back [J].
Gebauer, Fatima ;
Preiss, Thomas ;
Hentze, Matthias W. .
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2012, 4 (07) :1-14
[10]   Histone Deacetylase 3 Promotes RCAN1 Stability and Nuclear Translocation [J].
Han, Kyung Ah ;
Kang, Hye Seon ;
Lee, Jee Won ;
Yoo, Lang ;
Im, Eunju ;
Hong, Ahyoung ;
Lee, Yun Ju ;
Shin, Woo Hyun ;
Chung, Kwang Chul .
PLOS ONE, 2014, 9 (08)