Precursor RNA processing 3 is required for male fertility, and germline stem cell self-renewal and differentiation via regulating spliceosome function in Drosophila testes
Precursor RNA processing 3 is required for male fertility, and germline stem cell self-renewal and differentiation via regulating spliceosome function in Drosophila testes
复制标题
前体 RNA 加工 3 是雄性生育力以及生殖系干细胞通过调节果蝇睾丸剪接体功能进行自我更新和分化所必需的
DOI：
10.1038/s41598-019-46419-x
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发表时间：
2019-07-10
影响因子：
4.6
通讯作者：
Yu, Jun
中科院分区：
文献类型：
--
作者：
Chen, Xia;Luan, Xiaojin;Yu, Jun
核前体mRNA剪接体是一个含有5个小的核核糖核蛋白颗粒（snRNP）和许多剪接因子的大复合体。信使RNA（mRNA）通过RNA剪接过程由前mRNA产生，这在真核生物中是保守的。前体RNA加工3（Prp 3）是一种与U4/U6相关的snRNP，其功能在很大程度上仍然未知。本研究通过果蝇睾丸模型的遗传操作，证实了Prp 3对果蝇雄性生育力的重要作用，生殖系干细胞（GSCs）和早期包囊细胞中Prp 3的缺失导致了果蝇睾丸结构异常，GSCs和包囊干细胞的维持缺陷。精原细胞和早期囊肿细胞中Prp 3的敲低介导分化缺陷引起的肿瘤形成体外实验表明，Prp 3基因敲低可抑制果蝇S2细胞的增殖，增加细胞死亡，并通过调节剪接体亚基的表达来控制剪接体的功能。我们还鉴定了Prp复合物中的另外两个剪接因子（Prp 19和Prp 8），它们在果蝇干细胞小生境中模拟了Prp 3的表型。我们的研究结果揭示了前体RNA加工因子在雄性睾丸中的重要作用，表明Prp 3是Prp复合物中的关键剪接体成分，通过调节果蝇睾丸中的剪接体功能，对雄性生育力和生殖系干细胞的自我更新和分化至关重要。
The nuclear pre-mRNA spliceosome is a large complex containing five small nuclear ribonucleoprotein particles (snRNPs) and many splicing factors. Messenger RNAs (mRNAs) are generated from pre-mRNAs by the process of RNA splicing, which is conserved in eukaryotes. Precursor RNA processing 3 (Prp3) is a U4/U6-associated snRNP whose function remains largely unknown. In the present study, using genetic manipulation of aDrosophila melanogastertestis model, we demonstrated thatPrp3is essential for male fertility inDrosophila.Prp3deficiency in germline stem cells (GSCs) and early cyst cells resulted in abnormal structure of testes and maintenance defects of GSCs and cyst stem cells. Knockdown ofPrp3in spermatogonia and early cyst cells mediated tumor formation caused by differentiation defects. Using anin vitroassay, knockdown ofPrp3decreased proliferation and increased cell death, and controlled the spliceosome function via regulating spliceosome subunits expression inDrosophilaS2 cells. We also identified two other splicing factors in the Prp complex (Prp19andPrp8), which mimicked the phenotype ofPrp3in theDrosophilastem cell niche. Our results revealed a significant role of precursor RNA processing factors in male testes, indicating that Prp3, a key spliceosome component in the Prp complex, is essential for male fertility, and germline stem cell self-renewal and differentiation, via regulating the spliceosome function inDrosophilatestes.