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Absence of Dbp2p Alters Both Nonsense-Mediated mRNA Decay and rRNA Processing

机译:Dbp2p的缺乏改变无义介导的mRNA衰变和rRNA加工。

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Dbp2p, a member of the large family of DEAD-box proteins and a yeast homolog of human p68, was shown to interact with Upf1p, an essential component of the nonsense-mediated mRNA decay pathway. Dbp2p:Upf1p interaction occurs within a large conserved region in the middle of Upf1p that is largely distinct from its Nmd2p and Sup35/45p interaction domains. Deletion of DBP2, or point mutations within its highly conserved DEAD-box motifs, increased the abundance of nonsense-containing transcripts, leading us to conclude that Dbp2p also functions in the nonsense-mediated mRNA decay pathway. Dbp2p, like Upf1p, acts before or at decapping, is predominantly cytoplasmic, and associates with polyribosomes. Interestingly, Dbp2p also plays an important role in rRNA processing. In dbp2Δ cells, polyribosome profiles are deficient in free 60S subunits and the mature 25S rRNA is greatly reduced. The ribosome biogenesis phenotype, but not the mRNA decay function, of dbp2Δ cells can be complemented by the human p68 gene. We propose a unifying model in which Dbp2p affects both nonsense-mediated mRNA decay and rRNA processing by altering rRNA structure, allowing specific processing events in one instance and facilitating dissociation of the translation termination complex in the other.
机译:Dbp2p是DEAD-box蛋白大家族的成员,是人p68的酵母同源物,被证明与Upf1p相互作用,Upf1p是无义介导的mRNA衰变途径的重要组成部分。 Dbp2p:Upf1p相互作用发生在Upf1p中间的一个大保守区域内,该区域与其Nmd2p和Sup35 / 45p相互作用域大不相同。删除 DBP2 或其高度保守的DEAD-box基序内的点突变,增加了无义转录物的丰度,使我们得出结论,Dbp2p在无义介导的mRNA衰变途径中也起作用。与Upf1p一样,Dbp2p在脱盖之前或之后起作用,主要是胞质的,并与多核糖体结合。有趣的是,Dbp2p在rRNA加工中也起着重要作用。在dbp2Δ细胞中,多核糖体谱缺少游离的60S亚基,成熟的25S rRNA大大降低。人类 p68 基因可以补充dbp2Δ细胞的核糖体生物发生表型,而不是mRNA的衰变功能。我们提出了一个统一的模型,其中Dbp2p通过改变rRNA结构来影响无义介导的mRNA降解和rRNA加工,在一种情况下允许发生特定的加工事件,而在另一种情况下促进翻译终止复合物的解离。

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