Mittra Bidyottam, Ray Dan S
Molecular Biology Institute, University of California, Los Angeles, 405 Hilgard Ave., Los Angeles, CA 90095-1570, USA.
Eukaryot Cell. 2004 Oct;3(5):1185-97. doi: 10.1128/EC.3.5.1185-1197.2004.
Crithidia fasciculata cycling sequence binding proteins (CSBP) have been shown to bind with high specificity to sequence elements present in several mRNAs that accumulate periodically during the cell cycle. The first described CSBP has subunits of 35.6 (CSBPA) and 42 kDa (CSBPB). A second distinct binding protein termed CSBP II has been purified from CSBPA null mutant cells, lacking both CSBPA and CSBPB proteins, and contains three major polypeptides with predicted molecular masses of 63, 44.5, and 33 kDa. Polypeptides of identical size were radiolabeled in UV cross-linking assays performed with purified CSBP II and 32P-labeled RNA probes containing six copies of the cycling sequence. The CSBP II binding activity was found to cycle in parallel with target mRNA levels during progression through the cell cycle. We have cloned genes encoding these three CSBP II proteins, termed RBP63, RBP45, and RBP33, and characterized their binding properties. The RBP63 protein is a member of the poly(A) binding protein family. Homologs of RBP45 and RBP33 proteins were found only among the kinetoplastids. Both RBP45 and RBP33 proteins and their homologs have a conserved carboxy-terminal half that contains a PSP1-like domain. All three CSBP II proteins show specificity for binding the wild-type cycling sequence in vitro. RBP45 and RBP33 are phosphoproteins, and RBP45 has been found to bind in vivo specifically to target mRNA containing cycling sequences. The levels of phosphorylation of both RBP45 and RBP33 were found to cycle during the cell cycle.
已证明束状短膜虫周期序列结合蛋白(CSBP)能高度特异性地结合细胞周期中周期性积累的几种mRNA中存在的序列元件。最早描述的CSBP有35.6 kDa的亚基(CSBPA)和42 kDa的亚基(CSBPB)。第二种不同的结合蛋白称为CSBP II,已从缺乏CSBPA和CSBPB蛋白的CSBPA基因敲除突变细胞中纯化出来,它包含三种主要多肽,预测分子量分别为63、44.5和33 kDa。在用纯化的CSBP II和含有六个周期序列拷贝的32P标记RNA探针进行的紫外线交联试验中,相同大小的多肽被放射性标记。发现CSBP II结合活性在细胞周期进程中与靶mRNA水平平行变化。我们克隆了编码这三种CSBP II蛋白的基因,分别称为RBP63、RBP45和RBP33,并对它们的结合特性进行了表征。RBP63蛋白是聚腺苷酸结合蛋白家族的成员。仅在动基体目生物中发现了RBP45和RBP33蛋白的同源物。RBP45和RBP33蛋白及其同源物都有一个保守的羧基末端,其中包含一个类似PSP1的结构域。所有三种CSBP II蛋白在体外对结合野生型周期序列都具有特异性。RBP45和RBP33是磷蛋白,并且已发现RBP45在体内能特异性结合含有周期序列的靶mRNA。发现RBP4�和RBP33的磷酸化水平在细胞周期中呈周期性变化。