Mutations in the Spliceosomal Gene ZRSR2 in Myelodysplastic Syndromes
Technical Report,01 Apr 2017,31 Mar 2018
Cedars-Sinai Medical Center Los Angeles United States
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This study focusses on ZRSR2, one of the recurrently mutated spliceosome genes in MDS. Our results demonstrate the importance of ZRSR2 to 012-type intron splicing, and identify candidate ZRSR2 targets that might mediate ZRSR2 pathogenic functions in MDS. We are using RNA-seq to comprehensively characterize the mis-splicing events driven by ZRSR2 mutations. To understand the mechanisms associated with ZRSR2 012-type intrans splicing, and the downstream pathways affected by ZRSR2 loss, we are identifying ZRSR2 binding partners, as well as pathways that can synergize with loss of ZRSR2 to promote MDS development. As ZRSR2 and TET2 mutations often cooccur in MDS, we are examining the mechanisms underpinning the cooperativity between ZRSR2 and TET2 mutations in myeloid transformation. Further, we are identifying and evaluating drugs that might selectively kill ZRSR2 mutated cells. Our long team goal is to provide a better understudying of the role of aberrant splicing in MDS, and to leverage this knowledge to develop new therapeutic modalities that specifically target cells with splicing factor mutations.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology