Alternative Splicing

Mis-spliced transcripts generate de novo proteins in TDP-43-related ALS/FTD

Summary This study demonstrates that loss of TDP-43 function leads to widespread cryptic splicing events that produce novel protein isoforms not normally expressed in healthy cells. These de novo proteins may contribute to the pathogenesis of ALS and FTD by triggering immune responses or impairing cellular functions.

Retention of CD19 intron 2 contributes to CART-19 resistance in leukemias with subclonal frameshift mutations in CD19

Summary This study identifies intron 2 retention in CD19 transcripts as a mechanism contributing to CAR-T19 therapy resistance in leukemias harboring subclonal frameshift mutations in CD19. The findings reveal how alternative splicing can undermine antigen-targeted cancer immunotherapy.