Létoquart Juliette, van Tran Nhan, Caroline Vonny, Aleksandrov Alexey, Lazar Noureddine, van Tilbeurgh Herman, Liger Dominique, Graille Marc
Laboratoire de Biochimie, CNRS, UMR 7654, Ecole Polytechnique, F-91128 Palaiseau Cedex, France Fonction et Architecture des Assemblages Macromoléculaires, Département B3S, Institut de Biologie Intégrative de la Cellule (I2BC), CNRS, UMR 9198, CEA, Université Paris Sud, F-91405 Orsay Cedex, France.
Laboratoire de Biochimie, CNRS, UMR 7654, Ecole Polytechnique, F-91128 Palaiseau Cedex, France.
Nucleic Acids Res. 2015 Dec 15;43(22):10989-1002. doi: 10.1093/nar/gkv1009. Epub 2015 Oct 4.
Most of the factors involved in translation (tRNA, rRNA and proteins) are subject to post-transcriptional and post-translational modifications, which participate in the fine-tuning and tight control of ribosome and protein synthesis processes. In eukaryotes, Trm112 acts as an obligate activating platform for at least four methyltransferases (MTase) involved in the modification of 18S rRNA (Bud23), tRNA (Trm9 and Trm11) and translation termination factor eRF1 (Mtq2). Trm112 is then at a nexus between ribosome synthesis and function. Here, we present a structure-function analysis of the Trm9-Trm112 complex, which is involved in the 5-methoxycarbonylmethyluridine (mcm(5)U) modification of the tRNA anticodon wobble position and hence promotes translational fidelity. We also compare the known crystal structures of various Trm112-MTase complexes, highlighting the structural plasticity allowing Trm112 to interact through a very similar mode with its MTase partners, although those share less than 20% sequence identity.
大多数参与翻译过程的因子（转运RNA、核糖体RNA和蛋白质）都经历转录后和翻译后修饰，这些修饰参与核糖体和蛋白质合成过程的精细调控。在真核生物中，Trm112作为至少四种甲基转移酶（MTase）的必需激活平台，这些甲基转移酶参与18S核糖体RNA（Bud23）、转运RNA（Trm9和Trm11）以及翻译终止因子eRF1（Mtq2）的修饰。因此，Trm112处于核糖体合成与功能的交汇点。在此，我们展示了Trm9-Trm112复合物的结构-功能分析，该复合物参与转运RNA反密码子摆动位置的5-甲氧羰基甲基尿苷（mcm(5)U）修饰，从而提高翻译保真度。我们还比较了各种Trm112-MTase复合物的已知晶体结构，突出了结构可塑性，这使得Trm112能够通过非常相似的模式与其MTase伙伴相互作用，尽管这些伙伴的序列同一性低于20%。
