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Drosophila ELYS regulates Dorsal dynamics during development.
Journal of Biological Chemistry ( IF 5.5 ) Pub Date : 2020-01-15 , DOI: 10.1074/jbc.ra119.009451
Saurabh Jayesh Kumar Mehta 1 , Vimlesh Kumar 2 , Ram Kumar Mishra 1
Affiliation  

Embryonic large molecule derived from yolk sac (ELYS) is a constituent protein of nuclear pores. It initiates assembly of nuclear pore complexes into functional nuclear pores toward the end of mitosis. Using cellular, molecular, and genetic tools, including fluorescence and Electron microscopy, quantitative PCR, and RNAi-mediated depletion, we report here that the ELYS ortholog (dElys) plays critical roles during Drosophila development. dElys localized to the nuclear rim in interphase cells, but during mitosis it was absent from kinetochores and enveloped chromatin. We observed that RNAi-mediated dElys depletion leads to aberrant development and, at the cellular level, to defects in the nuclear pore and nuclear lamina assembly. Further genetic analyses indicated that dElys depletion re-activates the Dorsal (NF-κB) pathway during late larval stages. Re-activated Dorsal caused untimely expression of the Dorsal target genes in the post-embryonic stages. We also demonstrate that activated Dorsal triggers apoptosis during later developmental stages by up-regulating the pro-apoptotic genes reaper and hid The apoptosis induced by Reaper and Hid was probably the underlying cause for developmental abnormalities observed upon dElys depletion. Moreover, we noted that dElys has conserved structural features, but contains a noncanonical AT-hook-like motif through which it strongly binds to DNA. Together, our results uncover a novel epistatic interaction that regulates Dorsal dynamics by dElys during development.

中文翻译:

果蝇ELYS调节发育过程中的背动态。

卵黄囊(ELYS)衍生的胚胎大分子是核孔的组成蛋白。它在有丝分裂末期开始将核孔复合体组装成功能性核孔。使用细胞,分子和遗传工具,包括荧光和电子显微镜,定量PCR和RNAi介导的耗竭,我们在这里报告ELYS直系同源基因(dElys)在果蝇发育过程中起关键作用。dElys定位于相间细胞的核边缘,但在有丝分裂过程中,动植物和包膜染色质均不存在。我们观察到,RNAi介导的dElys耗竭会导致异常发育,并在细胞水平上导致核孔和核层板组装中的缺陷。进一步的遗传分析表明,dElys耗竭在幼虫后期重新激活了背侧(NF-κB)途径。重新激活的背侧导致胚胎后阶段背侧靶基因的过时表达。我们还证明了激活的背突通过上调促凋亡基因reaper和hid触发了发育后期的凋亡。Reaper和Hid诱导的凋亡可能是dElys耗竭后观察到发育异常的根本原因。此外,我们注意到dElys具有保守的结构特征,但包含非规范的AT钩样基序,可通过其牢固地与DNA结合。在一起,我们的结果揭示了一种新的上位相互作用,该相互作用在发育过程中通过dElys调节背动态。我们还证明了激活的背突通过上调促凋亡基因reaper和hid触发了发育后期的凋亡。Reaper和Hid诱导的凋亡可能是dElys耗竭后观察到发育异常的根本原因。此外,我们注意到dElys具有保守的结构特征,但包含非规范的AT钩样基序,可通过其牢固地与DNA结合。在一起,我们的结果揭示了一种新的上位相互作用,该相互作用在发育过程中通过dElys调节背动态。我们还证明了激活的背突通过上调促凋亡基因reaper和hid触发了发育后期的凋亡。Reaper和Hid诱导的凋亡可能是dElys耗竭后观察到发育异常的根本原因。此外,我们注意到dElys具有保守的结构特征,但包含非规范的AT钩样基序,可通过其牢固地与DNA结合。在一起,我们的结果揭示了一种新的上位相互作用,该相互作用在发育过程中通过dElys调节背动态。但包含非规范的AT钩样基序,通过它可以牢固地与DNA结合。在一起,我们的结果揭示了一种新的上位相互作用,该相互作用在发育过程中通过dElys调节背动态。但包含非规范的AT钩样基序,通过它可以牢固地与DNA结合。在一起,我们的结果揭示了一种新的上位相互作用,该相互作用在发育过程中通过dElys调节背动态。
更新日期:2020-02-21
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