Ptch/SPOUT1 甲基转移酶在 28S rRNA 上沉积 m7G 修饰，以维持果蝇和人类正常的核糖体功能。
The Ptch/SPOUT1 methyltransferase deposits an mU modification on 28 rRNA for normal ribosomal function in flies and humans.
作者信息
Chen Jie, Bai Yaofu, Huang Yuantai, Cui Min, Wang Yiqing, Gu Zhenqi, Wu Xiaolong, Li Yubin, Rong Yikang S
机构信息
MOE Key Lab of Rare Pediatric Diseases, Hengyang College of Medicine, University of South China, Hengyang, China.
Plant Protection Research Institute, Guangdong Academy of Agricultural Sciences, Guangdong Provincial Key Laboratory of High Technology for Plant Protection, Guangzhou, China.
出版信息
Sci Adv. 2024 Dec 13;10(50):eadr1743. doi: 10.1126/sciadv.adr1743.
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 modified uridine base (mU) was identified to be present on the 28 rRNA from humans and frogs but absent in bacteria or yeast. Here, we show that the equivalent mU is present in 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, -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.
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王国的许多rRNA修饰的位点、功能和酶学有了深入了解，但对于许多并非普遍存在的修饰，我们仍缺乏基本认识。一种单一的N修饰尿苷碱基（mU）被确定存在于人类和青蛙的28S rRNA上，但在细菌或酵母中不存在。在这里，我们表明在[具体生物]中存在等效的mU，并且Ptch/CG12128酶及其人类同源物SPOUT1对于进行这种修饰都是必要且充分的。经Ptch修饰的U位于大核糖体亚基的一个功能中心，一致地，[具体生物]-突变细胞会出现核糖体功能丧失。SPOUT1被认为是人类中最具药物可及性的RNA甲基转移酶，它代表了一个独特的靶点，在癌细胞中核糖体功能可能会被特异性损害。
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