1 research outputs found
Zrsr2 and functional U12-dependent spliceosome are necessary for follicular development
SUMMARY
ZRSR2 is a splicing factor involved in recognition of 30
-intron splice sites that is
frequently mutated in myeloid malignancies and several tumors; however, the
role of mutations of Zrsr2 in other tissues has not been analyzed. To explore the bio logical role of ZRSR2,we generated threeZrsr2 mutantmouse lines. AllZrsr2 mutant
lines exhibited blood cell anomalies, and in two lines, oogenesis was blocked at the
secondary follicle stage. RNA-seq of Zrsr2mu secondary follicles showed aberrations
in gene expression and showed altered alternative splicing (AS) events involving
enrichment of U12-type intron retention (IR), supporting the functional Zrsr2 action
in minor spliceosomes. IR events were preferentially associated with centriole repli cation, protein phosphorylation, and DNA damage checkpoint. Notably, we found
alterations in AS events of 50 meiotic genes. These results indicate that ZRSR2 mu tations alter splicing mainly in U12-type introns, which may affect peripheral blood
cells, and impede oogenesis and female fertility