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Abstract Mutation or deletion of the U1 snRNP-associated factor LUC7L2 is associated with myeloid neoplasms, and knockout of LUC7L2 alters cellular metabolism. Here, we show that members of the LUC7 protein family differentially regulate two major classes of 5′ splice sites (5′SS) and broadly regulate mRNA splicing in both human cell lines and leukemias with LUC7L2 copy number variation.
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