The PINc domain protein Utp24, a putative nuclease, is required for the early cleavage steps in 18S rRNA maturation
The PINc domain protein Utp24, a putative nuclease, is required for the early cleavage steps in 18S rRNA maturation
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DOI：
10.1073/pnas.0603673103
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发表时间：
2006-06-20
影响因子：
11.1
通讯作者：
Baserga, Susan J.
中科院分区：
文献类型：
--
作者：
Bleichert, Franziska;Grannemant, Sander;Baserga, Susan J.
核糖体生物合成是一个复杂的过程，需要超过150个反式作用因子，其中许多形成与核糖体本身一样大和复杂的大分子组装。这些复合物之一，SSU加工体，是前185 rRNA成熟所必需的。虽然它的许多成分已经被鉴定，但切割前18 S rRNA的内切酶仍然是个谜。在这里，我们研究了四个以前未知的PINc结构域蛋白，这是预测作为核酸酶的功能，在酵母核糖体生物合成的作用。在我们的分析中，我们还包括Utp 23，一种与PINc结构域蛋白Utp 24同源的蛋白。我们的研究结果表明，Utp 23和Utp 24是必需的核仁蛋白和以前未描述的组件的SSU加工体。从这个意义上说，Utp 23和Utp 24都是18 S rRNA成熟过程中前三个切割步骤所必需的。此外，在保守的推定活性位点Utp 24，但不是Utp 23的单点突变废除其在核糖体生物合成的功能。我们的研究结果表明Utp 24可能是在位点A和/或A（2）切割前体rRNA的难以捉摸的核酸内切酶。
Ribosome biogenesis is a complex process that requires > 150 transacting factors, many of which form macromolecular assemblies as big and complex as the ribosome itself. One of those complexes, the SSU processome, is required for pre-185 rRNA maturation. Although many of its components have been identified, the endonucleases that cleave the pre-18S rRNA have remained mysterious. Here we examine the role of four previously uncharacterized PINc domain proteins, which are predicted to function as nucleases, in yeast ribosome biogenesis. We also included Utp23, a protein homologous to the PINc domain protein Utp24, in our analysis. Our results demonstrate that Utp23 and Utp24 are essential nucleolar proteins and previously undescribed components of the SSU processome. In that sense, both Utp23 and Utp24 are required for the first three cleavage steps in 18S rRNA maturation. In addition, single-point mutations in the conserved putative active site of Utp24 but not Utp23 abrogate its function in ribosome biogenesis. Our results suggest that Utp24 might be the elusive endonuclease that cleaves the pre-rRNA at sites A, and/or A(2).