表达无催化活性的核蛋白 dyskerin 的小鼠胚胎成纤维细胞中 rRNA 生长缓慢且不稳定，缺乏假尿嘧啶核苷。
Slow growth and unstable ribosomal RNA lacking pseudouridine in mouse embryonic fibroblast cells expressing catalytically inactive dyskerin.
机构信息
Department of Pediatrics and Division of Hematology, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, PA 19104-4318, USA.
出版信息
FEBS Lett. 2013 Jul 11;587(14):2112-7. doi: 10.1016/j.febslet.2013.05.028. Epub 2013 May 28.
Abstract
Pseudouridine is the most abundant modified nucleotide in ribosomal RNA throughout eukaryotes and archaea but its role is not known. Here we produced mouse embryonic fibroblast cells expressing only catalytically inactive dyskerin, the pseudouridine synthase that converts uridine to pseudouridine in ribosomal RNA. The mutant dyskerin protein, D125A, was extremely unstable but cells were able to divide and grow very slowly. Abnormalities in ribosome RNA synthesis were apparent but mature cytoplasmic RNAs lacking pseudouridine were produced and were very unstable. We conclude that pseudouridine is required to stabilize the secondary structure of ribosomal RNA that is essential for its function.
摘要
假尿嘧啶核苷是真核生物和古菌核糖体 RNA 中含量最丰富的修饰核苷酸，但它的作用尚不清楚。在这里，我们构建了仅表达无催化活性的突变型人端粒酶 RNA 结合蛋白（dyskerin）的小鼠胚胎成纤维细胞，该蛋白是将尿嘧啶转化为核糖体 RNA 中假尿嘧啶核苷的假尿嘧啶合酶。突变的 dyskerin 蛋白 D125A 极不稳定，但细胞仍能分裂并缓慢生长。核糖体 RNA 合成异常，但缺乏假尿嘧啶的成熟细胞质 RNA 被合成且极不稳定。我们的结论是，假尿嘧啶核苷对于稳定核糖体 RNA 的二级结构是必需的，而后者对于核糖体 RNA 的功能至关重要。
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