DDX6 Orchestrates Mammalian Progenitor Function through the mRNA Degradation and Translation Pathways.
DDX6 Orchestrates Mammalian Progenitor Function through the mRNA Degradation and Translation Pathways.
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DOI：
10.1016/j.molcel.2015.08.014
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发表时间：
2015-10-01
期刊：
影响因子：
16
通讯作者：
Sen GL
中科院分区：
文献类型：
--
作者：
Wang Y;Arribas-Layton M;Chen Y;Lykke-Andersen J;Sen GL
在成体组织中，干细胞和祖细胞必须平衡增殖和分化以维持体内平衡。如何做到这一点尚不清楚。在这里，我们表明，死亡盒RNA解旋酶，DDX 6是维持成人祖细胞功能所必需的。DDX 6缺失导致表皮祖细胞的过早分化和增殖降低。为了维持自我更新，DDX 6与YBX 1结合，结合在增殖/自我更新调节因子（CDK 1，EZH 2）的3′非翻译区（UTR）中发现的茎环，并将其招募到EIF 4 E以促进其翻译。DDX 6通过调控分化诱导转录因子KLF 4的5′UTR，并通过与mRNA降解蛋白结合降解其转录产物，防止祖细胞的过早分化。我们的研究结果表明，DDX 6复合物通过两种不同的途径维持祖细胞功能，包括降解分化诱导转录本以及促进自我更新和增殖mRNA的翻译。
In adult tissues, stem and progenitor cells must balance proliferation and differentiation to maintain homeostasis. How this is done is unclear. Here, we show that the DEAD box RNA helicase, DDX6 is necessary for maintaining adult progenitor cell function. DDX6 loss results in premature differentiation and decreased proliferation of epidermal progenitor cells. To maintain self-renewal, DDX6 associates with YBX1 to bind the stem loops found in the 3′ untranslated regions (UTRs) of regulators of proliferation/self-renewal (CDK1, EZH2) and recruit them to EIF4E to facilitate their translation. To prevent premature differentiation of progenitor cells, DDX6 regulates the 5′UTR of differentiation inducing transcription factor, KLF4 and degrades its transcripts through association with mRNA degradation proteins. Our results demonstrate that progenitor function is maintained by DDX6 complexes through two distinct pathways which include the degradation of differentiation inducing transcripts as well as promoting the translation of self-renewal and proliferation mRNAs.