mRNA-Decapping Associated DcpS Enzyme Controls Critical Steps of Neuronal Development.
mRNA-Decapping Associated DcpS Enzyme Controls Critical Steps of Neuronal Development.
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mRNA 脱帽相关 DcpS 酶控制神经元发育的关键步骤。
DOI：
10.1093/cercor/bhab302
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Kiledjian,
中科院分区：
文献类型：
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作者：
Salamon,Iva;Palsule,Geeta;Luo,Xiaobing;Roque,Alfonso;Tucai,Shawn;Khosla,Ishan;Volk,Nicole;Liu,Wendy;Cui,Huijuan;Pozzo,ValentinaDal;Zalamea,Petronio;Jiao,Xinfu;D'Arcangelo,Gabriella;Hart,RonaldP;Rasin,Mladen-Roko;Kiledjian,
编码清道夫 mRNA 脱帽酶 DcpS 的基因中的纯合突变已被证明是发育迟缓和智力障碍的基础。智力障碍与新皮质发育异常和 mRNA 代谢相关。然而，DcpS 及其清除剂脱帽活性在神经元发育中的作用尚不清楚。在这里，我们发现源自具有 DcpS 突变的患者的人类神经元的分化和神经突生长受到损害。此外，在发育中的小鼠新皮质中，DcpS对于径向迁移、极性、神经突生长和发育中谷氨酸能神经元的识别是必需的。总的来说，这些发现表明，清除剂 mRNA 脱帽活性在神经发育中发挥多种关键作用，并进一步证实 mRNA 代谢和新皮质病理与智力障碍有关。
Homozygous mutations in the gene encoding the scavenger mRNA-decapping enzyme, DcpS, have been shown to underlie developmental delay and intellectual disability. Intellectual disability is associated with both abnormal neocortical development and mRNA metabolism. However, the role of DcpS and its scavenger decapping activity in neuronal development is unknown. Here, we show that human neurons derived from patients with a DcpS mutation have compromised differentiation and neurite outgrowth. Moreover, in the developing mouse neocortex, DcpS is required for the radial migration, polarity, neurite outgrowth, and identity of developing glutamatergic neurons. Collectively, these findings demonstrate that the scavenger mRNA decapping activity contributes to multiple pivotal roles in neural development and further corroborate that mRNA metabolism and neocortical pathologies are associated with intellectual disability.