Full-length transcript alterations in human bronchial epithelial cells withU2AF1S34F mutations

• DOI: 10.26508/lsa.202000641
• Publication Date: 2023-07-27T17:48:12Z
• Authors: Cameron M Soulette; Eva Hrabeta-Robinson; Carlos Arevalo; Colette Felton; Alison D Tang; Maximillian G Marin; Angela N Brooks
• Keywords: Nonsense-Mediated Decay

U2AF1 is one of the most recurrently mutated splicing factors in lung adenocarcinoma and has been shown to cause transcriptome-wide pre-mRNA alterations; however, full-length altered mRNA isoforms associated with mutation are largely unknown. To better understand impact on isoform fate function, we conducted high-throughput long-read cDNA sequencing from isogenic human bronchial epithelial cells without a S34F mutation. We identified 49,366 multi-exon transcript isoforms, more than half which did not match GENCODE or short-read–assembled isoforms. found 198 significant expression usage changes relative WT, only 68% were assembled by short reads. Expression immune-related genes down-regulated mutant observed changes. Finally, reveal that likely targeted nonsense-mediated decay cells, suggesting may alter translational output those affected genes. Altogether, our work provides resource cells.