Structural insights into mRNA reading frame regulation by tRNA modification and slippery codon-anticodon pairing.
Structural insights into mRNA reading frame regulation by tRNA modification and slippery codon-anticodon pairing.
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DOI：
10.7554/elife.51898
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发表时间：
2020-10-05
期刊：
影响因子：
7.7
通讯作者：
Dunham CM
中科院分区：
文献类型：
--
作者：
Hoffer ED;Hong S;Sunita S;Maehigashi T;Gonzalez RL Jnr;Whitford PC;Dunham CM
TRNA反密码子环中与三核苷酸反密码子相邻的修饰通过稳定tRNA来影响翻译保真度，从而允许准确读取信使核糖核酸遗传密码。一个例子是位于反密码子环中的鸟嘌呤核苷酸37(M1G37)上的N1-甲基鸟苷修饰，并且直接邻近反密码子核苷酸34、35、36。TRNAPro中m1G37的缺失导致多核苷酸、光滑密码子上+1的移码。在这里，我们报道了含有tRNAPro的细菌核糖体与同源密码子或光滑密码子结合的结构，以确定m1G37修饰如何阻止mRNA移码。这些结构表明，某些密码子-反密码子背景和m1G37的缺失破坏了tRNAPro与核糖体P位的相互作用，导致了通常只有在EF-G介导的mRNA-tRNA对易位过程中才能看到的大的构象变化。这些研究为m1G37如何在滑动的mRNA密码子的背景下稳定tRNAPro与核糖体的相互作用提供了分子见解。
Modifications in the tRNA anticodon loop, adjacent to the three-nucleotide anticodon, influence translation fidelity by stabilizing the tRNA to allow for accurate reading of the mRNA genetic code. One example is the N1-methylguanosine modification at guanine nucleotide 37 (m1G37) located in the anticodon loop andimmediately adjacent to the anticodon nucleotides 34, 35, 36. The absence of m1G37 in tRNAPro causes +1 frameshifting on polynucleotide, slippery codons. Here, we report structures of the bacterial ribosome containing tRNAPro bound to either cognate or slippery codons to determine how the m1G37 modification prevents mRNA frameshifting. The structures reveal that certain codon–anticodon contexts and the lack of m1G37 destabilize interactions of tRNAPro with the P site of the ribosome, causing large conformational changes typically only seen during EF-G-mediated translocation of the mRNA-tRNA pairs. These studies provide molecular insights into how m1G37 stabilizes the interactions of tRNAPro with the ribosome in the context of a slippery mRNA codon.