Sequence interval within the PEST motif of Bicoid is important for translational repression of caudal mRNA in the anterior region of the Drosophila embryo

Sequence interval within the PEST motif of Bicoid is important for translational repression of caudal mRNA in the anterior region of the Drosophila embryo
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DOI:
10.1093/emboj/18.7.1966
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发表时间:
1999-04-01
期刊:
影响因子:
11.4
通讯作者:
Rivera-Pomar, R
Rivera-Pomar, R
中科院分区:
生物学1区
文献类型:
--
作者:
Niessing, D;Dostatni, N;Rivera-Pomar, R

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果蝇体组织蛋白Bicoid(Bcd)是一种母系同源结构域蛋白。它形成了一个浓度梯度沿着的纵轴preblastoderm胚胎和激活早期合子分割基因在一个阈值依赖的方式,此外,Bcd作为一个翻译阻遏物的母体尾部(cad)mRNA在前区的胚胎。通过共转染实验,我们发现Bcd以帽依赖的方式抑制翻译,Bcd依赖的翻译抑制涉及Bcd的PEST基序的一部分,PEST基序是一个保守的蛋白质基序,在蛋白质降解中起重要作用。Bcd缺陷的胚胎表达转基因衍生的Bcd突变体的救援实验表明,PEST基序的C-末端部分内的氨基酸替换防止cad mRNA的翻译抑制,但允许Bcd依赖的转录激活。因此,Bcd含有可分离的蛋白质结构域,用于靶基因的转录和翻译调控。母体来源的钙蛋白在胚胎的前部区域干扰头部形态发生,表明钙蛋白mRNA的抑制Bcd是一个重要的控制事件,在早期果蝇胚胎发生。
The Drosophila body organizer Bicoid (Bcd) is a maternal homeodomain protein. It forms a concentration gradient along the longitudinal axis of the preblastoderm embryo and activates early zygotic segmentation genes in a threshold-dependent fashion, In addition, Bcd acts as a translational repressor of maternal caudal (cad) mRNA in the anterior region of the embryo. This process involves a distinct Bcd-binding region (BBR) in the 3' untranslated region (UTR) of cad mRNA, Using cotransfection assays, we found that Bcd represses translation in a cap-dependent manner, Bcd-dependent translational repression involves a portion of the PEST motif of Bcd, a conserved protein motif best known for its function in protein degradation. Rescue experiments with Bcd-deficient embryos expressing transgene-derived Bcd mutants indicate that amino acid replacements within the C-terminal portion of the PEST motif prevent translational repression of cad mRNA but allow for Bcd-dependent transcriptional activation. Thus, Bcd contains separable protein domains for transcriptional and translational regulation of target genes. Maternally-derived cad protein in the anterior region of embryos interferes with head morphogenesis, showing that cad mRNA suppression by Bcd is an important control event during early Drosophila embryogenesis.