Long read direct RNA-sequencing of human monocyte derived macrophages for chimeric RNA discovery

Whether mRNA can contain exons from geographically distinct genes to form chimeric mRNA in the absence of malignancy is widely unknown. Pervasive and naturally occurring chimeric mRNA could greatly expand the functional diversity of mammalian transcriptomes and potentially generate novel hybrid proteins that underpin diverse biological processes.

Here we demonstrate that long-read direct RNA-seq, paired with targeted mRNA splice-isoform analysis, enables the identification of a plethora of dynamically regulated chimeric mRNA in innate immune cells.