Zamore P D, Williamson J R, Lehmann R
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139, USA.
RNA. 1997 Dec;3(12):1421-33.
Translation of hunchback(mat) (hb[mat]) mRNA must be repressed in the posterior of the pre-blastoderm Drosophila embryo to permit formation of abdominal segments. This translational repression requires two copies of the Nanos Response Element (NRE), a 16-nt sequence in the hb[mat] 3' untranslated region. Translational repression also requires the action of two proteins: Pumilio (PUM), a sequence-specific RNA-binding protein; and Nanos, a protein that determines the location of repression. Binding of PUM to the NRE is thought to target hb(mat) mRNA for repression. Here, we show the RNA-binding domain of PUM to be an evolutionarily conserved, 334-amino acid region at the carboxy-terminus of the approximately 158-kDa PUM protein. This contiguous region of PUM retains the RNA-binding specificity of full-length PUM protein. Proteins with sequences homologous to the PUM RNA-binding domain are found in animals, plants, and fungi. The high degree of sequence conservation of the PUM RNA-binding domain in other far-flung species suggests that the domain is an ancient protein motif, and we show that conservation of sequence reflects conservation of function: that is, the homologous region from a human protein binds RNA with sequence specificity related to but distinct from Drosophila PUM.
驼背（母体）（hb[mat]）mRNA的翻译必须在前胚盘期果蝇胚胎的后部受到抑制，以允许腹部体节的形成。这种翻译抑制需要两个拷贝的纳米反应元件（NRE），它是hb[mat] 3'非翻译区中的一个16个核苷酸的序列。翻译抑制还需要两种蛋白质的作用：Pumilio（PUM），一种序列特异性RNA结合蛋白；以及纳米蛋白，一种决定抑制位置的蛋白质。PUM与NRE的结合被认为是将hb(mat) mRNA靶向进行抑制。在这里，我们表明PUM的RNA结合结构域是在约158 kDa的PUM蛋白羧基末端的一个进化上保守的、由334个氨基酸组成的区域。PUM的这个连续区域保留了全长PUM蛋白的RNA结合特异性。在动物、植物和真菌中发现了与PUM RNA结合结构域具有序列同源性的蛋白质。PUM RNA结合结构域在其他远缘物种中的高度序列保守性表明该结构域是一个古老的蛋白质基序，并且我们表明序列的保守反映了功能的保守：也就是说，来自人类蛋白质的同源区域以与果蝇PUM相关但不同的序列特异性结合RNA。
