Decapping reaction of mRNA requires Dcp1 in fission yeast: Its characterization in different species from yeast to human

Decapping reaction of mRNA requires Dcp1 in fission yeast: Its characterization in different species from yeast to human
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DOI:
10.1093/jb/mvh190
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发表时间:
2004-12-01
影响因子:
2.7
通讯作者:
Katada, T
Katada, T
中科院分区:
生物学4区
文献类型:
--
作者:
Sakuno, T;Araki, Y;Katada, T

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5‘帽结构的断裂参与了主要的5’到3'和无义介导的mRNA衰变途径,由Dcp1和Dcp2组成的蛋白质复合物已被确定为在酿酒酵母和人类中负责脱帽反应的物种。尽管体外研究表明Dcp2是一种催化活性成分,但Dcp1在脱帽反应中的作用仍有待于在除出芽酵母以外的生物中探索。为了阐明Dcp1依赖的脱帽机制,我们鉴定了cerevisiae Dcp1 (ScDcp1)在高等真核生物中的同源物,并分析了它们在不同物种中的功能。Shizosaccharomyces pombe SpDcp1可以抑制出芽酵母scdcp1基因破坏引起的生长缓慢和mRNA稳定表型,而人类同源物hDcp1则不能。相反,裂变酵母中由SpDcp1基因断裂引起的相同表型被hDcp1及其与SpDcp1相当的部分序列有效地补充。这些结果表明,Dcp2和Dcp1在mrna衰变途径中都起着不可或缺的作用,裂变酵母中依赖Dcp1的脱冠反应特征在萌发酵母到哺乳动物的mrna衰变机制进化中处于中间位置。
Cleavage of the 5'-cap structure is involved in the major 5'-to-3' and nonsense-mediated mRNA decay pathways, and the protein complex consisting of Dcp1 and Dcp2 has been identified as the species responsible for the decapping reaction in Saccharomyces cerevisiae and human. Although in vitro studies indicate that Dcp2 is catalytically an active component, the role of Dcp1 in the decapping reaction remains to be explored in organisms other than budding yeast. To elucidate the Dcp1-dependent decapping mechanisms, we identified the homologues of S. cerevisiae Dcp1 (ScDcp1) in higher eukaryotes and analyzed their functions in the different species. The phenotypes of slow growth and mRNA stabilization induced by Scdcp1-gene disruption in budding yeast could be suppressed by the Shizosaccharomyces pombe SpDcp1 but not by the human homologue hDcp1. In contrast, the same phenotypes caused by Spdcp1-gene disruption in fission yeast were effectively complemented by hDcp1 and its partial sequence comparable to SpDcp1. These results indicate that not only Dcp2 but also Dcp1 plays an indispensable role in mRNA-decay pathway and that the characteristics of Dcp1-dependent decapping reaction in fission yeast hold an intermediate position in the evolution of mRNA-decay machinery from budding yeast to mammals.