Downregulation of NHP2 promotes proper cyst formation in Drosophila ovary
Downregulation of NHP2 promotes proper cyst formation in Drosophila ovary
复制标题
DOI：
10.1111/dgd.12539
复制
发表时间：
2018-05
期刊：
影响因子：
4.6
通讯作者：
Shumpei Morita;Ryoma Ota;Satoru Kobayashi
中科院分区：
文献类型：
--
作者：
Shumpei Morita;Ryoma Ota;Satoru Kobayashi
在果蝇卵巢中，生殖干细胞（GSC）分裂产生两个子细胞。一个子细胞维持为GSC，而另一个子细胞启动囊肿形成，这是一个涉及形成2-，4-，8-和16-细胞囊肿的四次同步有丝分裂的过程。在这项研究中，我们发现NHP 2水平的降低，H/ACA小核仁核糖核蛋白复合物的一种组分，催化rRNA假尿苷酸化，促进向8细胞囊肿的进展。在包囊形成过程中，NHP 2蛋白主要集中在生殖细胞的核仁中。NHP 2表达以及核仁大小在从2细胞到4细胞囊肿的进展过程中突然下降。生殖系中NHP 2活性的降低导致4细胞和8细胞包囊的积累，并减少单细胞的数量。此外，NHP 2敲低损害了向16细胞包囊的转变。此外，由性致死性（Sxl）敲除引起的肿瘤表型（其特征在于单细胞和双细胞包囊的积累）通过NHP 2敲除而部分挽救。当Sxl和NHP 2活性同时受到抑制时，四细胞和八细胞包囊的数量增加。此外，在卵巢中，Sxl蛋白与NHP 2 mRNA物理相互作用。因此，可以合理地得出结论，Sxl在转录后水平抑制NHP 2活性以促进正确的包囊形成。由于NHP 2敲低不影响生殖细胞中的整体蛋白质合成，我们推测NHP 2依赖性假尿苷酸化的变化（参与特定mRNA的翻译）必须是完整的，以促进正确的囊肿形成。
In Drosophila ovary, germline stem cells (GSCs) divide to produce two daughter cells. One daughter is maintained as a GSC, whereas the other initiates cyst formation, a process involving four synchronous mitotic divisions that form 2‐, 4‐, 8‐, and 16‐cell cysts. In this study, we found that reduction in the level of NHP2, a component of the H/ACA small nucleolar ribonucleoprotein complex that catalyzes rRNA pseudouridylation, promotes progression to 8‐cell cysts. NHP2 protein was concentrated in the nucleoli of germline cells during cyst formation. NHP2 expression, as well as the nucleolar size, abruptly decreased during progression from 2‐cell to 4‐cell cysts. Reduction in NHP2 activity in the germline caused accumulation of 4‐ and 8‐cell cysts and decreased the number of single cells. In addition, NHP2 knockdown impaired the transition to 16‐cell cysts. Furthermore, a tumorous phenotype caused by Sex‐lethal (Sxl) knockdown, which is characterized by accumulation of single and two‐cell cysts, was partially rescued by NHP2 knockdown. When Sxl and NHP2 activities were concomitantly repressed, the numbers of four‐ and eight‐cell cysts were increased. In addition, Sxl protein physically interacted with NHP2 mRNA in ovaries. Thus, it is reasonable to conclude that Sxl represses NHP2 activity at the post‐transcriptional level to promote proper cyst formation. Because NHP2 knockdown did not affect global protein synthesis in the germarium, we speculate that changes in NHP2‐dependent pseudouridylation, which is involved in translation of specific mRNAs, must be intact in order to promote proper cyst formation.