PLX209905

GSE63816: Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant myelodysplastic syndrome

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Somatic mutations in the spliceosome gene ZRSR2 located on the X chromosome are associated with myelodysplastic syndrome (MDS). ZRSR2 is involved in the recognition of 3 splice site during the early stages of spliceosome assembly; however, its precise role in RNA splicing has remained unclear. Here, we characterize ZRSR2 as an essential component of the minor spliceosome (U12-dependent) assembly. shRNA mediated knockdown of ZRSR2 leads to impaired splicing of the U12-type introns, and RNA-Sequencing of MDS bone marrow reveals that loss of ZRSR2 activity causes increased mis-splicing. These splicing defects involve retention of the U12-type introns while splicing of the U2-type introns remain mostly unaffected. ZRSR2 deficient cells also exhibit reduced proliferation potential and distinct alterations in myeloid and erythroid differentiation in vitro. These data identify a specific role for ZRSR2 in RNA splicing and highlight dysregulated splicing of U12-type introns as a characteristic feature of ZRSR2 mutations in MDS. SOURCE: Henry Yang (csiyangh@nus.edu.sg) - Cancer Science Institute of Singapore