Long noncoding RNA MARL regulates antiviral responses through suppression miR-122-dependent MAVS downregulation in lower vertebrates

Abstract

Increasing evidence suggests important roles for long noncoding RNAs (lncRNAs) as new gene modulators involved in various biological processes. However, the function roles of lncRNAs in lower vertebrates are still unknown. Here, we firstly identify a lncRNA, named MAVS antiviral-related lncRNA (MARL), as a key regulator for antiviral immunity in teleost fish. The results indicate that fish MAVS play essential roles in host antiviral responses and inhibition ofSiniperca chuatsi rhabdovirus(SCRV) replication. miR-122 reduces MAVS expression and suppress MAVS-mediated antiviral responses, which may help viruses evade host antiviral responses. Further, MARL functions as a competing endogenous RNA (ceRNA) for miR-122 to control protein abundance of MAVS, thereby inhibiting SCRV replication and promoting antiviral responses. Our data not only shed new light on understanding the function role of lncRNA in biological processes in lower vertebrates, but confirmed the hypothesis that ceRNA regulatory networks exist widely in vertebrates. Author summary Increasing evidence indicates that lncRNAs participate in the regulation of various biological processes, especially innate and adaptive immunity. However, the relationship between lncRNAs and host antiviral responses remains largely unknown, particularly in lower vertebrates. Our results provided the first direct evidence that a lncRNA, termed MAVS antiviral-related lncRNA (MARL), acts as a key regulator for antiviral immunity in lower vertebrates. lncRNAs has been identified to function as competing endogenous RNAs (ceRNAs) and cross-talk with mRNAs by competing shared for miRNAs. Such ceRNAs regulate the distribution of miRNA molecules on their targets and thereby apply an additional level of post-transcriptional regulation. In our study, MARL functions as a ceRNA for miR-122 to control protein abundance of fish MAVS, thereby inhibiting virus replication and promoting antiviral responses. This is the first study to demonstrate ceRNA regulatory networks existing in lower vertebrates, which can provide new insights into understanding the effects of lncRNAs on host-virus interactions.