Journal Article

Unusual base pairing during the decoding of a stop codon by the ribosome

Wu, Guowei, Ng, Chyan Leong, Yu, Yi-Tao, Ramakrishnan, V., Fernández, Israel S., Kelley, Ann C.

2013

Overview

Here, the structure of the 30S ribosomal subunit and the 70S ribosome in complex with a messenger RNA with pseudouridine in the place of uridine reveals unexpected base pairing. Surprising base pairs fool ribosome When messenger RNA is translated into protein, the end of the protein-coding sequence is indicated by a three-base stop codon. Stop codons do not code for an amino acid, but recently it was shown that changing the first base to a pseudouridine (Ψ, the C-glycoside isomer of the nucleoside uridine) allows the incorporation of an amino acid, such that translation could continue past the stop codon. Venki Ramakrishnan and colleagues have determined the structure of the 30S ribosomal subunit in complex with an mRNA with ΨAG at the A site and a portion of serine transfer RNA. The structure reveals unexpected purine–purine base pairing at the first position of the codon and unusual pairing at the second and third positions. This study provides additional evidence for plasticity in the decoding centre of the ribosome. 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 pairs 1 . Here we determined the crystal structure at 3.1 Å resolution of the 30S ribosomal subunit in complex with the anticodon stem loop of tRNA Ser 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/337/1645/2570 / 631/337/574/1789 / 631/337/574/1793 / 631/535/1266 / Anticodon - chemistry / Anticodon - genetics / Anticodon - metabolism / Base Pairing / Base Sequence / Codon / Codon, Terminator - chemistry / Codon, Terminator - genetics / Codon, Terminator - metabolism / Crystallography, X-Ray / Deoxyribonucleic acid / DNA / Genes / Geometry / Humanities and Social Sciences / letter / Models, Molecular / multidisciplinary / Mutation / Nucleic Acid Conformation / Properties / Protein biosynthesis / Protein Conformation / Protein synthesis / Pseudouridine - chemistry / Pseudouridine - genetics / Pseudouridine - metabolism / Purines / Ribosome Subunits, Small, Bacterial - chemistry / Ribosome Subunits, Small, Bacterial - genetics / Ribosome Subunits, Small, Bacterial - metabolism / Ribosomes / Ribosomes - chemistry / Ribosomes - genetics / Ribosomes - metabolism / RNA, Transfer, Ser - chemistry / RNA, Transfer, Ser - genetics / RNA, Transfer, Ser - metabolism / Science / Transfer RNA