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首页> 外文期刊>Journal of Molecular Biology >No19 Is a Spatial Regulator for the Human ITS2 Pre-rRNA Endonuclease-Kinase Complex
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No19 Is a Spatial Regulator for the Human ITS2 Pre-rRNA Endonuclease-Kinase Complex

机译：NO19是人体ITS2前rRNA内切核酸酶 - 激酶复合物的空间调节剂

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摘要

The ribosome plays a universal role in translating the cellular proteome. Defects in the ribosome assembly factor Las1L are associated with congenital lethal motor neuron disease and X-linked intellectual disability disorders, yet its role in processing precursor ribosomal RNA (pre-rRNA) is largely unclear. The Las1L endoribonuclease associates with the No19 polynucleotide kinase to form the internal transcribed spacer 2 (ITS2) pre-rRNA endonuclease kinase machinery. Together, Las1L No19 catalyzes RNA cleavage and phosphorylation to mark the ITS2 for degradation. While ITS2 processing is critical for the production of functional ribosomes, the regulation of mammalian Las1L No19 remains obscure. Here we characterize the human Las1L No19 complex and identify critical molecular features that regulate its assembly and spatial organization. We establish that Las1L and No19 form a higher-order complex and identify the regions responsible for orchestrating this intricate architecture. Structural analysis by high-resolution imaging defines the intricate spatial pattern of Las1L No19 within the nucleolar sub-structure linked with late pre-rRNA processing events. Furthermore, we uncover a No19-encoded nucleolar localization sequence that is responsible for nucleolar transport of the assembled Las1L No19 complex. Together, these data provide a mechanism for the assembly and nucleolar localization of the human ITS2 pre-rRNA endonuclease kinase complex. Published by Elsevier Ltd.
机译：核糖体在平移细胞蛋白质组中起普遍作用。核糖体组装因子LAS11中的缺陷与先天性致命运动神经元疾病和X链接智力疾病有关，但其在加工前体核糖体RNA（PRE-RRNA）中的作用很大程度上不清楚。 LAS11上型核酸酶与NO19多核苷酸激酶相关联，以形成内转录的间隔件2（IT2）预rRNA内切核酸酶激酶机械。一起，LAS11 NO19催化RNA切割和磷酸化以标记其2的降解。虽然ITS2加工对于生产功能性核糖体至关重要，但哺乳动物LAS1L NO19的调节仍然模糊不清。在这里，我们描述了人LAS1L No19复合物，并确定了调节其组装和空间组织的临界分子特征。我们建立了LAS1L和NO19，形成了一个高阶的复杂，并确定负责协调这种复杂架构的地区。高分辨率成像结构分析定义了与晚期前rRNA处理事件的核聚体亚结构内的LAS1L NO19中的复杂空间模式。此外，我们发现了No19编码的核仁定位序列，该序列负责组装的LAS11 No19复合物的核仁传输。这些数据在一起提供了一种机制，用于组装和核仁定位的人IS2预rRNA内切核酸酶激酶复合物的机制。 elsevier有限公司出版

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