A new circular RNA–encoded protein BIRC6-236aa inhibits transmissible gastroenteritis virus (TGEV)–induced mitochondrial dysfunction

作者：Xiaomin Zhao, Jianxiong Guo, Xinyue Wang, Jiadi Lin, Zhihao Liu, Chunmei Xu, Di Zhang, Dewen Tong · 发表于：Journal of Biological Chemistry · 年份：2022 · DOI：10.1016/j.jbc.2022.102280 · 被引用次数：9 · 研究领域：Circular RNAs in diseases、MicroRNA in disease regulation、GDF15 and Related Biomarkers

Transmissible gastroenteritis virus (TGEV), a member of the coronavirus family, is the pathogen responsible for transmissible gastroenteritis, which results in mitochondrial dysfunction in host cells. Previously, we identified 123 differentially expressed circular RNAs (cRNA)from the TGEV-infected porcine intestinal epithelial cell line jejunum 2 (IPEC-J2). Previous bioinformatics analysis suggested that, of these, circBIRC6 had the potential to regulate mitochondrial function. Furthermore, mitochondrial permeability transition, a key step in the process of mitochondrial dysfunction, is known to be caused by abnormal opening of mitochondrial permeability transition pores (mPTPs) regulated by the voltage-dependent anion-selective channel protein 1 (VDAC)–Cyclophilin D (CypD) complex. Therefore, in the present study, we investigated the effects of circBIRC6-2 on mitochondrial dysfunction and opening of mPTPs. We found that TGEV infection reduced circBIRC6-2 levels, which in turn reduced mitochondrial calcium (Ca 2+ ) levels, the decrease of mitochondrial membrane potential, and opening of mPTPs. In addition, we also identified ORFs and internal ribosomal entrance sites within the circBIRC6-2 RNA. We demonstrate circBIRC6-2 encodes a novel protein, BIRC6-236aa, which we show inhibits TGEV-induced opening of mPTPs during TGEV infection. Mechanistically, we identified an interaction between BIRC6-236aa and VDAC1, suggesting that BIRC6-236aa destabilizes the VDAC1–CypD complex. Tak...