The ribosomal RNA (rRNA) is one of the most heavily modified RNA species in nature. Although we have advanced knowledge of the sites, functions, and the enzymology of many of the rRNA modifications from all kingdoms of life, we lack basic understanding of many of those that are not universally present. A single N 3 modified uridine base (m 3 U) was identified to be present on the 28 S rRNA from humans and frogs but absent in bacteria or yeast. Here, we show that the equivalent m 3 U is present in Drosophila and that the Ptch/CG12128 enzyme and its human homolog SPOUT1 are both necessary and sufficient for carrying out the modification. The Ptch-modified U is at a functional center of the large ribosomal subunit, and, consistently, ptch -mutant cells suffer loss of ribosomal functions. SPOUT1, suggested to be the most druggable RNA methyltransferases in humans, represents a unique target where ribosomal functions could be specifically compromised in cancer cells.

中文翻译：

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Ptch/SPOUT1 甲基转移酶在 28 S rRNA 上沉积一个 m 3 U 修饰，以实现果蝇和人类的正常核糖体功能


核糖体 RNA （rRNA） 是自然界中修饰程度最高的 RNA 种类之一。尽管我们对来自所有生命界的许多 rRNA 修饰的位点、功能和酶学都有深入的了解，但我们对许多并非普遍存在的修饰缺乏基本了解。经鉴定，单个 N 3 修饰尿苷碱基 （m 3 U） 存在于人类和青蛙的 28 S rRNA 上，但在细菌或酵母中不存在。在这里，我们表明果蝇中存在等效的 m 3 U，并且 Ptch/CG12128 酶及其人类同源物 SPOUT1 对于进行修饰既必要又充分。Ptch 修饰的 U 位于大核糖体亚基的功能中心，并且始终存在 ptch 突变细胞的核糖体功能丧失。SPOUT1 被认为是人类中最具成药性的 RNA 甲基转移酶，代表了癌细胞中核糖体功能可能受到特异性损害的独特靶标。