Trm112 Is Required for Bud23-Mediated Methylation of the 18S rRNA at Position G1575
Trm112 Is Required for Bud23-Mediated Methylation of the 18S rRNA at Position G1575
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DOI：
10.1128/mcb.06623-11
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发表时间：
2012-06-01
影响因子：
5.3
通讯作者：
Heurgue-Hamard, Valerie
中科院分区：
文献类型：
--
作者：
Figaro, Sabine;Wacheul, Ludivine;Heurgue-Hamard, Valerie
众所周知，大分子的转录后和翻译后修饰可以微调其功能。 Trm112 是独特的，可作为 tRNA 和蛋白质甲基转移酶的激活剂。在此，我们报道在酿酒酵母中，Trm112 是有效核糖体合成和有丝分裂进展所必需的。 Trm112 与前 rRNA 和多种核糖体合成反式作用因子（包括 18S rRNA 甲基转移酶 Bud23）共纯化。与Trm112激活甲基转移酶的已知机制一致，我们发现Trm112在体外直接与Bud23相互作用，并且这是其在体内稳定性所必需的。因此，trm112 Delta 细胞缺乏 Bud23 介导的 G1575 位置的 18S rRNA 甲基化和小核糖体亚基的形成。 Bud23 未能结合新生前核糖体，会激活涉及 TRAMP 复合物的核仁监视途径，导致前核糖体降解。因此，Trm112 在 rRNA、tRNA 和翻译因子修饰中具有活性，理想地将其置于核糖体合成和功能之间的界面。
Posttranscriptional and posttranslational modification of macromolecules is known to fine-tune their functions. Trm112 is unique, acting as an activator of both tRNA and protein methyltransferases. Here we report that in Saccharomyces cerevisiae, Trm112 is required for efficient ribosome synthesis and progression through mitosis. Trm112 copurifies with pre-rRNAs and with multiple ribosome synthesis trans-acting factors, including the 18S rRNA methyltransferase Bud23. Consistent with the known mechanisms of activation of methyltransferases by Trm112, we found that Trm112 interacts directly with Bud23 in vitro and that it is required for its stability in vivo. Consequently, trm112 Delta cells are deficient for Bud23-mediated 18S rRNA methylation at position G1575 and for small ribosome subunit formation. Bud23 failure to bind nascent preribosomes activates a nucleolar surveillance pathway involving the TRAMP complexes, leading to preribosome degradation. Trm112 is thus active in rRNA, tRNA, and translation factor modification, ideally placing it at the interface between ribosome synthesis and function.