CircBIRC6-2 inhibits transmissible gastroenteritis virus induced mitochondrial permeability transition pore opening by its encoding protein

ABSTRACT: Transmissible gastroenteritis virus (TGEV), a member of coronavirus, is the pathogen of TGE. We previously found 123 circular RNAs (circRNAs) were differential expression during activation of mitochondrial permeability transition in porcine intestinal epithelial cells-jejunum 2 cell line (IPEC-J2) in response to TGEV infection. Mitochondrial permeability transition pore (mPTP) is a transmembrane pore of mitochondria and plays a key role in MPT. mPTP abnormal opening causes MPT. Therefore, we postulated that circRNAs might be related to mPTP abnormal opening induced by TGEV. In this study, we found that circBIRC6-2 could inhibit the mPTP abnormal opening induced by TGEV. Interestingly, circBIRC6-2 encodes protein BIRC6-236aa. An open reading frame (ORF) and internal ribosomal entrance site (IRES) of circBIRC6-2 were identified. We also found that BIRC6-236aa rather than circBIRC6-2 inhibited the mPTP opening by overexpression of circBIRC6-2 related vectors. We obtained 91 proteins that interacted with BIRC6-236aa using immunoprecipitation-mass spectrometry (IP-MS). The interaction between voltage-dependent anion-selective channel protein 1 (VDAC1) and BIRC6-236aa was demonstrated through co-immunoprecipitation (Co-IP). Moreover, BIRC6-236aa could inhibit the formation of VDAC1 and Cyclophilin D (CypD) complexes. Overall, these results indicated that BIRC6-236aa antagonized mPTP opening by interacting with VDAC1 to weaken the extent of interaction between VDAC1 and CypD.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Sus Scrofa Domesticus (domestic Pig)

TISSUE(S): Jejunum

SUBMITTER: Xiaomin Zhao  

LAB HEAD: Xiaomin Zhao

PROVIDER: PXD029055 | Pride | 2022-10-13

REPOSITORIES: Pride