Identification and analysis of lncRNA50877, which is involved in KRT8-mediated mitochondrial homeostasis and GCRV replication in grass carp (Ctenopharyngodon idella).
Grass carp (Ctenopharyngodon idella) reovirus (GCRV), the causative agent of hemorrhagic disease, causes substantial economic losses in the grass carp industry every year. However, the biological regulatory roles of long non-coding RNAs (lncRNAs) during GCRV infection remain largely unclear. In this study, high-throughput sequencing technology was used to analyze the expression profiles of lncRNAs in GCRV-infected and mock-infected liver and intestinal tissues of grass carp. In this study, compared with those in the control group, the transcriptomic profiles of grass carp after GCRV genotype II (HZ08 strain) infection revealed 742 upregulated and 1,259 downregulated lncRNA transcripts in the intestines, whereas 709 upregulated and 1,513 downregulated lncRNA transcripts were identified in the liver. GO and KEGG pathway analyses indicated that these lncRNAs were enriched primarily in pathways associated with biological process regulation, including "Pyruvate metabolism" and the "AMPK signaling pathway". Notably, we revealed that lncRNA50877 (PX600394) was upregulated in grass carp tissues and CIK cells following GCRV infection. CIK cells infected with equal titers of GCRV in vitro for 24 h exhibited aggravated cytopathic effect (CPE) upon lncRNA50877 overexpression. Furthermore, ChIRP-MS and RNA pull-down assays confirmed its direct interaction with KRT8 (keratin 8, PX531115). Our results demonstrated that lncRNA50877 disrupts mitochondrial homeostasis by negatively regulating KRT8 expression, thereby modulating ROS levels, apoptosis, and autophagy; promoting oxidative stress-induced cell injury; and providing favorable conditions for GCRV replication. In summary, lncRNA50877 may act as an autophagy-related lncRNA that regulates mitochondrial function and contributes to innate immune responses, offering new insights into the crosstalk between autophagy and innate immunity.