文章基本信息

标题：Zrsr2 and functional U12-dependent spliceosome are necessary for follicular development
本地全文：下载
作者：Isabel Gómez-Redondo ; Eva Pericuesta ; Paula Navarrete-Lopez 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：2
页码：1-22
DOI：10.1016/j.isci.2022.103860
语种：English
出版社：Elsevier
摘要：SummaryZRSR2 is a splicing factor involved in recognition of 3′-intron splice sites that is frequently mutated in myeloid malignancies and several tumors; however, the role of mutations ofZrsr2in other tissues has not been analyzed. To explore the biological role of ZRSR2, we generated threeZrsr2mutant mouse lines. AllZrsr2mutant lines exhibited blood cell anomalies, and in two lines, oogenesis was blocked at the secondary follicle stage. RNA-seq ofZrsr2musecondary follicles showed aberrations in gene expression and showed altered alternative splicing (AS) events involving enrichment of U12-type intron retention (IR), supporting the functionalZrsr2action in minor spliceosomes. IR events were preferentially associated with centriole replication, protein phosphorylation, and DNA damage checkpoint. Notably, we found alterations in AS events of 50 meiotic genes. These results indicate that ZRSR2 mutations alter splicing mainly in U12-type introns, which may affect peripheral blood cells, and impede oogenesis and female fertility.Graphical abstractDisplay OmittedHighlights•Zrsr2mumice allow us to identify functions of Zrsr2in vivo•Minor splicing factor Zrsr2 is essential for oogenesis and peripheral blood cells•Zrsr2 impairment affects the splicing of U12-type intron-containing genes•Zrsr2muaberrant splicing causes a global alteration of gene expressionBiological sciencesMolecular biologyTranscriptomics