Xrn1/Pacman affects apoptosis and regulates expression of hid and reaper.
Xrn1/Pacman affects apoptosis and regulates expression of hid and reaper.
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DOI：
10.1242/bio.201410199
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发表时间：
2015-04-02
期刊：
影响因子：
2.4
通讯作者：
Newbury SF
中科院分区：
文献类型：
--
作者：
Waldron JA;Jones CI;Towler BP;Pashler AL;Grima DP;Hebbes S;Crossman SH;Zabolotskaya MV;Newbury SF
程序性细胞死亡或凋亡是一种高度保守的细胞过程，对于正常发育以及环境应激下的组织稳态至关重要。细胞凋亡的失调与许多发育缺陷和疾病如肿瘤形成、自身免疫性疾病和神经系统疾病有关。在本文中，我们展示了一个新的作用，外切核糖核酸酶Pacman/Xrn 1在调节细胞凋亡。使用果蝇翅成虫盘作为一个模型系统，我们表明，在pacman无效突变的结果在小成虫盘以及在化蛹过程中的致死性。突变的翅盘显示出细胞凋亡的数量增加，特别是在翅袋区域。补偿性增殖也发生在这些突变的光盘，但这是不够的，以补偿细胞凋亡的同时增加。pacman无效突变的表型效应通过删除促凋亡基因reaper、hid和grim中的每一个的一个拷贝而得以挽救，这表明pacman通过这一途径起作用。无效pacman突变还导致促凋亡mRNAs，hid和reaper的表达显著增加，这种增加主要发生在转录后水平，表明Pacman通常靶向这些mRNAs进行降解。我们的研究结果揭示了保守的核糖核酸外切酶Pacman的一种新功能，并表明这种核糖核酸外切酶在其他生物体的细胞凋亡调控中是重要的。
Programmed cell death, or apoptosis, is a highly conserved cellular process that is crucial for tissue homeostasis under normal development as well as environmental stress. Misregulation of apoptosis is linked to many developmental defects and diseases such as tumour formation, autoimmune diseases and neurological disorders. In this paper, we show a novel role for the exoribonuclease Pacman/Xrn1 in regulating apoptosis. Using Drosophila wing imaginal discs as a model system, we demonstrate that a null mutation in pacman results in small imaginal discs as well as lethality during pupation. Mutant wing discs show an increase in the number of cells undergoing apoptosis, especially in the wing pouch area. Compensatory proliferation also occurs in these mutant discs, but this is insufficient to compensate for the concurrent increase in apoptosis. The phenotypic effects of the pacman null mutation are rescued by a deletion that removes one copy of each of the pro-apoptotic genes reaper, hid and grim, demonstrating that pacman acts through this pathway. The null pacman mutation also results in a significant increase in the expression of the pro-apoptotic mRNAs, hid and reaper, with this increase mostly occurring at the post-transcriptional level, suggesting that Pacman normally targets these mRNAs for degradation. Our results uncover a novel function for the conserved exoribonuclease Pacman and suggest that this exoribonuclease is important in the regulation of apoptosis in other organisms.
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