LAS1L interacts with the mammalian Rix1 complex to regulate ribosome biogenesis.
LAS1L interacts with the mammalian Rix1 complex to regulate ribosome biogenesis.
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DOI：
10.1091/mbc.e11-06-0530
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发表时间：
2012-02
影响因子：
3.3
通讯作者：
Denicourt C
中科院分区：
文献类型：
--
作者：
Castle CD;Cassimere EK;Denicourt C
ETOC：核糖体合成是一个多步骤的过程，在核仁中起始，转录前体rRNA，其经历一系列修饰和加工步骤以产生成熟rRNA。在本文中，我们描述了一种新的60 S核糖体生物合成复合物与LAS1L，控制rRNA加工和合成的28 S rRNA。RNA聚合酶I转录与前rRNA加工、前核糖体颗粒组装和核输出的协调是一个精细调节的过程，需要许多辅助因子的协同作用。然而，这些蛋白质中的一些的确切功能以及它们如何组装成亚复合物仍然不清楚。LAS1L首先被描述为60S前核糖体亚基成熟所需的核仁蛋白。在本文中，我们证明，LAS 1 L相互作用PELP 1，TEX10，和WDR 18，哺乳动物的同源物的芽殖酵母Rix 1复合物，沿着与NOL 9和SENP 3，形成一个新的核仁复合物，cofractionates与60 S前核糖体亚基。LAS1L相关蛋白的缺失导致p53依赖性G1期阻滞，并导致前rRNA内部转录间隔区2区域的加工缺陷。我们进一步表明，该复合物的核仁定位需要活性RNA聚合酶I转录和小泛素样修饰特异性蛋白酶SENP 3。两者合计，我们的数据确定了一种新的哺乳动物复杂的60 S核糖体亚基合成所需的，提供了进一步深入了解复杂的，但描述不佳，在高等真核生物的核糖体生物合成过程。
ETOC: Ribosome synthesis is a multistep process initiated in the nucleolus with the transcription of a precursor rRNA that is subjected to a series of modification and processing steps to generate the mature rRNA. In this paper, we describe a novel 60S ribosome biogenesis complex associating with LAS1L that controls rRNA processing and synthesis of the 28S rRNA. The coordination of RNA polymerase I transcription with pre-rRNA processing, preribosomal particle assembly, and nuclear export is a finely tuned process requiring the concerted actions of a number of accessory factors. However, the exact functions of some of these proteins and how they assemble in subcomplexes remain poorly defined. LAS1L was first described as a nucleolar protein required for maturation of the 60S preribosomal subunit. In this paper, we demonstrate that LAS1L interacts with PELP1, TEX10, and WDR18, the mammalian homologues of the budding yeast Rix1 complex, along with NOL9 and SENP3, to form a novel nucleolar complex that cofractionates with the 60S preribosomal subunit. Depletion of LAS1L-associated proteins results in a p53-dependent G1 arrest and leads to defects in processing of the pre-rRNA internal transcribed spacer 2 region. We further show that the nucleolar localization of this complex requires active RNA polymerase I transcription and the small ubiquitin-like modifier–specific protease SENP3. Taken together, our data identify a novel mammalian complex required for 60S ribosomal subunit synthesis, providing further insight into the intricate, yet poorly described, process of ribosome biogenesis in higher eukaryotes.