BACKGROUND Protein phosphatase 1 (PP1) is involved in diverse cellular processes, and is targeted to substrates via interaction with many different protein binding partners. PP1 catalytic subunits (PP1c) fall into PP1alpha and PP1beta subfamilies based on sequence analysis, however very few PP1c binding proteins have been demonstrated to discriminate between PP1alpha and PP1beta. RESULTS URI (unconventional prefoldin RPB5 interactor) is a conserved molecular chaperone implicated in a variety of cellular processes, including the transcriptional response to nutrient signalling and maintenance of DNA integrity. We show that Drosophila Uri binds PP1alpha with much higher affinity than PP1beta, and that this ability to discriminate between PP1c forms is conserved to humans. Most Uri is cytoplasmic, however we found some protein associated with active RNAPII on chromatin. We generated a uri loss of function allele, and show that uri is essential for viability in Drosophila. uri mutants have transcriptional defects, reduced cell viability and differentiation in the germline, and accumulate DNA damage in their nuclei. CONCLUSION Uri is the first PP1alpha specific binding protein to be described in Drosophila. Uri protein plays a role in transcriptional regulation. Activity of uri is required to maintain DNA integrity and cell survival in normal development.

中文翻译：

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果蝇 Uri 是一种 PP1α 结合蛋白，对于活力、维持 DNA 完整性和正常转录活性至关重要。


背景蛋白磷酸酶 1 (PP1) 参与多种细胞过程，并通过与许多不同的蛋白质结合配偶体相互作用而靶向底物。根据序列分析，PP1 催化亚基 (PP1c) 属于 PP1alpha 和 PP1beta 亚家族，但很少有 PP1c 结合蛋白被证明能够区分 PP1alpha 和 PP1beta。结果 URI（非常规前折叠蛋白 RPB5 相互作用蛋白）是一种保守的分子伴侣，参与多种细胞过程，包括对营养信号传导的转录反应和 DNA 完整性的维持。我们发现，果蝇 Uri 与 PP1alpha 的结合亲和力比 PP1beta 的亲和力高得多，并且这种区分 PP1c 形式的能力对于人类来说是保守的。大多数 Uri 是细胞质的，但我们在染色质上发现了一些与活性 RNAPII 相关的蛋白质。我们生成了 uri 功能缺失等位基因，并表明 uri 对于果蝇的生存能力至关重要。 uri 突变体具有转录缺陷，降低细胞活力和生殖系分化，并在细胞核中积累 DNA 损伤。结论 Uri 是果蝇中第一个被描述的 PP1α 特异性结合蛋白。 Uri 蛋白在转录调控中发挥作用。 uri 的活性是维持 DNA 完整性和正常发育中细胞存活所必需的。