Detection of chimeric alpha-defensin transcripts and peptides in mouse Paneth cells.

INTRODUCTION: In mammals, Paneth cells, located in the crypts of the small intestine, produceantimicrobial peptides that serve to keep the intestinal microbiome under control. a-Defensins are the primary antimicrobial peptides produced by these cells. METHODS: We used 148 publicly available bulk RNA-seq samples on purified PCs, proteomics on enriched purified PC proteins and Defa peptide activity assays to detect all Defa transcrips, including potential chimeric transcrips. RESULTS: We identified 28 expressed Defa genes in mice, with up to 85% of Paneth cell RNA reads mapping to these genes. Chimeric mRNAs, involving sequences from two different Defa genes, were detected in most experiments. Despite their low abundance (less than 0.3%), mass spectrometry confirmed the presence of chimeric peptides. Synthetic versions of these peptides demonstrated antibacterial activity against multiple bacterial species. CONCLUSION: We show the existence of chimeric Defa transcripts and peptides in mice that are biologically active. We propose a possible stochatic mechanism or that the activation of the UPR patway may play a role in their production.