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对“死亡终点”定位和活性的调控——该蛋白在拮抗微小RNA功能中的作用启示

Control of Dead end localization and activity--implications for the function of the protein in antagonizing miRNA function.

作者信息

Slanchev Krasimir, Stebler Juerg, Goudarzi Mehdi, Cojocaru Vlad, Weidinger Gilbert, Raz Erez

机构信息

Max-Planck-Institute for Biophysical Chemistry, Germ Cell Development, Am Fassberg 11, 37070 Goettingen, Germany.

出版信息

Mech Dev. 2009 Mar-Apr;126(3-4):270-7. doi: 10.1016/j.mod.2008.10.006. Epub 2008 Oct 25.

Abstract

Dead end (dnd) is a vertebrate-specific component of the germ plasm and germ-cell granules that is crucial for germ-cell development in zebrafish and mouse. Dnd counteracts the inhibitory function of miRNAs, thereby facilitating the expression of proteins such as Nanos and Tdrd7 in the germ cells. Here, we show that cis-acting elements within dnd mRNA and the RNA recognition motive (RRM) of the protein are essential for targeting protein expression to the germ cells and to the perinuclear granules, respectively. We demonstrate that as it executes its function, Dnd translocates between the germ-cell nucleus and germ-cell granules. This phenomenon is not observed in proteins mutated in the RRM motif, correlating with loss of function of Dnd. Based on molecular modeling, we identify the putative RNA binding domain of Dnd as a canonical RRM and propose that this domain is important for protein subcellular localization and function.

摘要

“死胡同”(Dead end,dnd)是生殖质和生殖细胞颗粒中的一种脊椎动物特有的成分,对斑马鱼和小鼠的生殖细胞发育至关重要。Dnd可抵消微小RNA(miRNAs)的抑制功能,从而促进生殖细胞中诸如Nanos和Tdrd7等蛋白质的表达。在此,我们表明dnd信使核糖核酸(mRNA)内的顺式作用元件以及该蛋白质的RNA识别基序(RRM)分别对于将蛋白质表达靶向生殖细胞和核周颗粒至关重要。我们证明,在执行其功能时,Dnd在生殖细胞核和生殖细胞颗粒之间易位。在RRM基序中发生突变的蛋白质中未观察到这种现象,这与Dnd功能丧失相关。基于分子建模,我们将Dnd的推定RNA结合结构域鉴定为典型的RRM,并提出该结构域对于蛋白质亚细胞定位和功能很重要。

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