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 peptide activity assays to detect all transcrips, including potential chimeric transcrips.

Results: We identified 28 expressed genes in mice, with up to 85% of Paneth cell RNA reads mapping to these genes. Chimeric mRNAs, involving sequences from two different 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 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.