Fig. 6: QKI-mediated alternative splicing events in genes critical to myofibrillogenesis.

A Representative RT-PCR confirmation of abnormal splicing events. All experiments are independently repeated at least three times with multiple independent sets of cell samples to confirm the reproducibility of the findings. B Schematic diagram of Skipped Exon events based on rMATs analysis. Solid lines indicated as normal splicing events, dash lines indicated as abnormal events in hCM-QKI^del. Relevant sashimi plots are in Supplementary Fig. 8. C RIP-qPCR analysis to verify the direct targets of QKI. Data were normalized to the IgG control group. Data represent the mean ± SEM from at least five independent experiments, statistical significance was determined by a two-tailed Student’s t-test. D Schematic diagram to demonstrate a premature STOP codon (i.e., TAA) in ACTN2^SE-8 mRNA in H1-8 mutant cells. To confirm that the NMD pathway is responsible for the downregulation of ACTN2^SE-8 in H1-8 mutant cells, H1-8 cardiomyocytes were treated overnight with NMDI14 (25 μM), followed by qRT-PCR analysis on the level of ACTN2^SE-8 in H1-8 cardiomyocytes. Data are shown as the mean ± SEM, statistical significance was determined by a two-tailed Student’s t-test.