Smaug recruits the CCR4/POP2/NOT deadenylase complex to trigger maternal transcript localization in the early drosophila embryo
Smaug recruits the CCR4/POP2/NOT deadenylase complex to trigger maternal transcript localization in the early drosophila embryo
复制标题
DOI：
10.1016/j.cub.2005.01.048
复制
发表时间：
2005-02-22
期刊：
影响因子：
9.2
通讯作者：
Smibert, CA
中科院分区：
文献类型：
--
作者：
Semotok, JL;Cooperstock, RL;Smibert, CA
背景：mRNA在细胞内的不对称定位促进蛋白质合成的精确时空控制。虽然细胞骨架运输为基础的定位在果蝇卵子发生的特点，很少有人知道的机制，在早期胚胎定位母体RNA。一个这样的机制，称为“降解/保护”作用于母体Hsp 83成绩单，将它们从大量的细胞质，同时保护他们在后极plasma.Results：在这里，我们确定的RNA结合蛋白，Smaug，以前被称为翻译抑制nanos，作为一个关键的调节器的降解/保护为基础的转录本定位。在Smaug突变体中，Hsp 83转录物的降解不被触发，因此，不发生定位。Hsp 83转录物在含有Smaug的mRNP复合物中，但Smaug不抑制Hsp 83 mRNA。相反，Smaug与CCR 4/POP 2/NOT去腺苷酶物理相互作用，将其募集到Hsp 83 mRNA以触发转录物去腺苷化和降解。当Smaug在体内靶向异源稳定的报告基因转录物时，这些转录物被去腺苷化和去稳定化。删除编码CCR 4的基因的缺失在功能丧失和功能获得背景下均表现出与Smaug的剂量敏感性相互作用。CCR 4蛋白水平的降低会损害Hsp 83转录本的不稳定性。结论：Smaug通过招募CCR 4/POP 2/NOT去腺苷酶触发特定母体转录本的不稳定性和定位。相反，Smaug介导的翻译抑制是通过Smaug和eIF 4 E之间的间接相互作用完成的，eIF 4 E是基本翻译机制的一个组成部分。因此，Smaug是一种多功能的转录后调节因子，其采用不同的机制来抑制翻译并诱导靶转录物的降解。
Background: Asymmetric localization of mRNAs within cells promotes precise spatio-temporal control of protein synthesis. Although cytoskeletal transport-based localization during Drosophila oogenesis is well characterized, little is known about the mechanisms that operate to localize maternal RNAs in the early embryo. One such mechanism-termed "degradation/protection" acts on maternal Hsp83 transcripts, removing them from the bulk cytoplasm while protecting them in the posterior pole plasm.Results: Here, we identify the RNA binding protein, Smaug, previously known as a translational repressor of nanos, as a key regulator of degradation/protection-based transcript localization. In smaug mutants, degradation of Hsp83 transcripts is not triggered, and, thus, localization does not occur. Hsp83 transcripts are in an mRNP complex containing Smaug, but Smaug does not translationally repress Hsp83 mRNA. Rather, Smaug physically interacts with the CCR4/POP2/NOT deadenylase, recruiting it to Hsp83 mRNA to trigger transcript deadenylation and degradation. When Smaug is targeted to heterologous stable reporter transcripts in vivo, these are deadenylated and destabilized. A deletion that removes the gene encoding CCR4 exhibits dose-sensitive interactions with Smaug in both a loss-of-function and a gain-of-function context. Reduction of CCR4 protein levels compromises Hsp83 transcript destabilization.Conclusions: Smaug triggers destabilization and localization of specific maternal transcripts through recruitment of the CCR4/POP2/NOT deadenylase. In contrast, Smaug-mediated translational repression is accomplished via an indirect interaction between Smaug and eIF4E, a component of the basic translation machinery. Thus, Smaug is a multifunctional posttranscriptional regulator that employs distinct mechanisms to repress translation and to induce degradation of target transcripts.