The Ptch/SPOUT1 methyltransferase deposits an m3U modification on 28S rRNA for normal ribosomal function in flies and humans

文献类型： 外文期刊

第一作者： Chen, Jie

作者： Chen, Jie;Bai, Yaofu;Wang, Yiqing;Gu, Zhenqi;Wu, Xiaolong;Rong, Yikang S.;Chen, Jie;Huang, Yuantai;Cui, Min;Li, Yubin

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期刊名称：SCIENCE ADVANCES （ 影响因子：12.5； 五年影响因子：14.1 ）

ISSN： 2375-2548

年卷期： 2024 年 10 卷 50 期

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收录情况： SCI

摘要： 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 N3 modified uridine base (m3U) was identified to be present on the 28S rRNA from humans and frogs but absent in bacteria or yeast. Here, we show that the equivalent m3U 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.

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