Zinoviev Alexandra, Akum Yael, Yahav Tal, Shapira Michal
Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Mol Biochem Parasitol. 2012 Oct;185(2):127-36. doi: 10.1016/j.molbiopara.2012.08.001. Epub 2012 Aug 14.
DED1/VAS belong to the DEAD-box family of RNA helicases that are associated with translation initiation in higher eukaryotes. Here we report on two DED1/VAS homologs that were identified in the genome of Leishmania. The two paralogs include all the domains that are typical of DEAD-box proteins and a phylogenetic analysis suggests that their duplication predates the branching of DED1 and VAS, which took place along with the appearance of early metazoans. The two Leishmania DED1 paralogs complement a yeast strain that fails to express the endogenous DED1, suggesting that they are responsible for a similar function. This is also supported by RNAi-mediated silencing experiments performed in Trypanosoma brucei. The two proteins are functionally redundant, since defects in protein synthesis and cell growth arrest were observed only when both paralogs were eliminated. A partial stage-specific specialization is observed, as LeishDED1-2 is more abundant in promastigotes, whereas expression of LeishDED1-1 increases in amastigotes. Duplication of an essential gene usually offers a safety net against mutations but in this case it also generated two proteins with stage specific expression.
DED1/VAS属于RNA解旋酶的DEAD-box家族,与高等真核生物的翻译起始相关。在此,我们报道了在利什曼原虫基因组中鉴定出的两个DED1/VAS同源物。这两个旁系同源物包含DEAD-box蛋白的所有典型结构域,系统发育分析表明它们的复制早于DED1和VAS的分化,而后者是随着早期后生动物的出现而发生的。利什曼原虫的两个DED1旁系同源物可互补一个无法表达内源性DED1的酵母菌株,这表明它们具有相似的功能。在布氏锥虫中进行的RNA干扰介导的沉默实验也支持了这一点。这两种蛋白质在功能上是冗余的,因为只有当两个旁系同源物都被消除时,才会观察到蛋白质合成缺陷和细胞生长停滞。观察到部分阶段特异性特化,因为LeishDED1-2在前鞭毛体中更为丰富,而LeishDED1-1的表达在无鞭毛体中增加。一个必需基因的复制通常为防止突变提供了一个安全保障,但在这种情况下,它还产生了两种具有阶段特异性表达的蛋白质。