当信使RNA(mRNA)被翻译成蛋白时,蛋白编码序列的末端由一个“三碱基”终止密码子来指示。终止密码子不编码氨基酸,但最近的研究表明,将第一个碱基改为一个假尿苷(Ψ,核苷尿苷的C-糖苷异构体)将允许结合一个氨基酸,以使翻译能够越过终止密码子继续进行。Venki Ramakrishnan 及其同事确定了与一个 mRNA 形成复合物的30S 核糖体亚单元的结构,其中ΨAG在A点,并有一部分“丝氨酸转移RNA”。该结构显示了在该密码子的第一个位置上的出乎意料的“嘌呤-嘌呤”碱基对以及在第二和第三个位置上的异常配对。这项研究为核糖体的解码中心中的可塑性提供了新证据。
Nature doi:10.1038/nature12302
Unusual base pairing during the decoding of a stop codon by the ribosome
Israel S. Fernández, Chyan Leong Ng, Ann C. Kelley, Guowei Wu, Yi-Tao Yu & V. Ramakrishnan
During normal translation, the binding of a release factor to one of the three stop codons (UGA, UAA or UAG) results in the termination of protein synthesis. However, modification of the initial uridine to a pseudouridine (Ψ) allows efficient recognition and read-through of these stop codons by a transfer RNA (tRNA), although it requires the formation of two normally forbidden purine–purine base pairs1. Here we determined the crystal structure at 3.1 Å resolution of the 30S ribosomal subunit in complex with the anticodon stem loop of tRNASer bound to the ΨAG stop codon in the A site. The ΨA base pair at the first position is accompanied by the formation of purine–purine base pairs at the second and third positions of the codon, which show an unusual Watson–Crick/Hoogsteen geometry. The structure shows a previously unsuspected ability of the ribosomal decoding centre to accommodate non-canonical base pairs.