RNA-Seq analysis reveals the long noncoding RNAs associated with immunity in wild Myotis myotis bats.

Background: Bats possess a uniquely adapted immune system that enables them to live with viral infections without the expected maladies. The molecular basis and regulation of bats' immune response is still not fully understood. Long non-coding RNAs (lncRNAs) represent an emerging class of molecules with critical regulatory roles in multiple biological processes, including immunity. We hypothesise that lncRNA-based regulation in bats may enable them to limit disease and live with viral pathogens.

Results: We developed a lncRNA prediction pipeline to annotate the long non-coding transcriptome across multiple bat tissues and at the population level. Characterisation of our lncRNA dataset based on 100 blood transcriptomes from wild Myotis myotis bats revealed lower and more tissue-specific expression compared with coding genes, reduced GC content and shorter length distributions, consistent with lncRNA profiles observed in other species. Using WGCNA network analyses and gene ontology, we identified two mRNA-lncRNA co-expression modules in Myotis myotis associated with distinct immune response: one linked to T-cell activation and vial processes, and the other to inflammation. From these immune-related lncRNAs, we selected four candidates with high translational potential for regulating viral infections and inflammation. These include a newly identified lncRNA, BatLnc1, with potential antiviral functions; the M. myotis ortholog of TUG1, implicated in viral-host interactions; and well-known lncRNAs MALAT1 and NEAT1, recognised for their roles in inflammatory regulation.

Conclusions: We conducted the first ab initio prediction of lncRNAs in a non-model bat species, the wild-caught M. myotis. Our network analysis revealed significant variation in immune status among a subset of individuals, potentially due to pathogenic conditions. From these variations, we identified lncRNAs most likely associated with immune response in bats. This initial exploration lays the groundwork for future experimental validations of lncRNA functions, offering promising insights into their role in bat immunity.