CircGRIA1 shows an age-related increase in male macaque brain and regulates synaptic plasticity and synaptogenesis

Kaiyu Xu, Ying Zhang, Wandi Xiong, Zhongyu Zhang, Zhengbo Wang, Longbao Lv, Chao Liu, Zhengfei Hu, Yong-Tang Zheng, Lin Lu, Xin-Tian Hu and Jiali Li ()
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Kaiyu Xu: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences
Ying Zhang: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences
Wandi Xiong: Peking University
Zhongyu Zhang: Peking University
Zhengbo Wang: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences
Longbao Lv: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences
Chao Liu: Kunming Primate Research Center of the Chinese Academy of Sciences
Zhengfei Hu: Kunming Primate Research Center of the Chinese Academy of Sciences
Yong-Tang Zheng: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences
Lin Lu: Peking University
Xin-Tian Hu: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences
Jiali Li: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Circular RNAs (circRNAs) are abundant in mammalian brain and some show age-dependent expression patterns. Here, we report that circGRIA1, a conserved circRNA isoform derived from the genomic loci of α-mino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit Gria1, shows an age-related and male-specific increase in expression in the rhesus macaque prefrontal cortex and hippocampus. We show circGRIA1 is predominantly localized to the nucleus, and find an age-related increase in its association with the promoter region of Gria1 gene, suggesting it has a regulatory role in Gria1 transcription. In vitro and in vivo manipulation of circGRIA1 negatively regulates Gria1 mRNA and protein levels. Knockdown of circGRIA1 results in an age-related improvement of synaptogenesis, and GluR1 activity-dependent synaptic plasticity in the hippocampal neurons in males. Our findings underscore the importance of circRNA regulation and offer an insight into the biology of brain aging.

Date: 2020
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DOI: 10.1038/s41467-020-17435-7

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