RNA-mediated alternative splicing and polyadenylation shape immune responses underlying disease resistance to Pseudomonas plecoglossicida in Larimichthys crocea.

Abstract

Pseudomonas plecoglossicida, a highly infectious pathogen that causes visceral white nodular disease, severely impacts the aquaculture of Larimichthys crocea and other marine species. However, the RNA-mediated regulatory mechanisms underlying host resistance remain poorly understood. To elucidate the post-transcriptional basis of immune regulation during infection, we integrated PacBio Iso-Seq and Illumina RNA-seq to construct a high-quality full-length transcriptome of L. crocea. A total of 22,063 genes and 122,436 transcripts were identified, including novel isoforms, transcription factors, and long non-coding RNAs. Comparative analyses between resistant strain (RS) and commercial strain (CS) revealed widespread alternative splicing (AS) and alternative polyadenylation (APA) events. Infection enriched complement and coagulation cascades and induced pro-inflammatory cytokines, while cytokine levels were consistently lower in RS than in CS, indicating tighter immune control. Key cytokine regulation-related genes, such as LGALS9, IRF8 and MR1, exhibited notable variations in AS and APA. Our results indicate that L. crocea mitigates excessive inflammation through isoform selection and 3'UTR regulation, enabling effective pathogen clearance while maintaining cytokine homeostasis. This study provides the first systematic view of RNA-mediated regulation in fish responses to P. plecoglossicida infection and identifies LGALS9, IRF8, and MR1 as promising targets for immunization and resistance breeding in aquaculture.