METTL3 Dysregulates RNA Splicing by Translational Control of Splicing Factors via m 6A Modification in CLL

RNA splicing dysregulation is a hallmark of chronic lymphocytic leukemia (CLL). Although somatic mutations in SF3B1 or U1 snRNA present in >20% of CLL patients, general splicing defects cannot be fully explained by genetic alterations of spliceosome alone. We reported that splicing factors are upregulated at protein, but not RNA, level in CLL compared to normal B cells by an integrated transcriptomic and proteomic analysis. This highlights a post-transcriptional layer of regulation that controls the abundance of splicing factors and contributes to RNA splicing dysregulation in CLL, with mechanism that has yet to be elucidated.