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在神经发育过程中,CCR4-NOT 去腺苷酸酶复合物亚基的表达模式不同。

Distinct expression patterns of the subunits of the CCR4-NOT deadenylase complex during neural development.

机构信息

Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

出版信息

Biochem Biophys Res Commun. 2011 Jul 29;411(2):360-4. doi: 10.1016/j.bbrc.2011.06.148. Epub 2011 Jun 28.

Abstract

The stability of mRNA influences the dynamics of gene expression. The mammalian CCR4-NOT complex is associated with deadenylase activity, which shortens the mRNA poly(A) tail and thereby contributes to destabilization of mRNAs. The complex consists of at least nine subunits and predominantly forms a 2.0MDa protein complex in HeLa cells. Accumulating evidence suggests that the CCR4-NOT complex is involved in cell growth and survival; however, the regulatory mechanisms of its biological activity remain obscure. Here, we analyzed the expression levels of the subunits of the CCR4-NOT complex in various mouse tissues and found that they showed distinct expression patterns. CNOT6, 6L, 7, and 10 were expressed nearly ubiquitously, whereas others were expressed in tissue-specific manners, such as those displaying especially high expression in the brain. Furthermore, CNOT2, 3, 6, and 8 were rapidly downregulated during differentiation of neural stem cells. These findings suggest that subunit composition of the CCR4-NOT complex differs among tissues and is altered during neural development, thereby imparting an additional layer of specificity in the control of gene expression.

摘要

mRNA 的稳定性影响基因表达的动力学。哺乳动物的 CCR4-NOT 复合物与脱腺苷酸酶活性相关,该酶缩短了 mRNA 的 poly(A)尾巴,从而导致 mRNA 的不稳定性。该复合物由至少九个亚基组成,在 HeLa 细胞中主要形成一个 2.0MDa 的蛋白质复合物。越来越多的证据表明,CCR4-NOT 复合物参与细胞的生长和存活;然而,其生物学活性的调节机制尚不清楚。在这里,我们分析了 CCR4-NOT 复合物的亚基在各种小鼠组织中的表达水平,发现它们表现出不同的表达模式。CNOT6、6L、7 和 10 几乎普遍表达,而其他亚基则以组织特异性的方式表达,例如在大脑中表达特别高的那些亚基。此外,神经干细胞分化过程中 CNOT2、3、6 和 8 的表达迅速下调。这些发现表明 CCR4-NOT 复合物的亚基组成在不同组织中存在差异,并在神经发育过程中发生改变,从而在基因表达的调控中赋予了额外的特异性。

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