Structure of the mammalian ribosome as it decodes the selenocysteine UGA codon

The elongation of eukaryotic selenoproteins relies on a poorly understood process of interpreting in-frame UGA stop codons as selenocysteine (Sec). We used cryo-electron microscopy to visualize Sec UGA recoding in mammals. A complex between the noncoding Sec-insertion sequence (SECIS), SECIS-binding protein 2 (SBP2), and 40S ribosomal subunit enables Sec-specific elongation factor eEFSec to deliver Sec. eEFSec and SBP2 do not interact directly but rather deploy their carboxyl-terminal domains to engage with the opposite ends of the SECIS. By using its Lys-rich and carboxyl-terminal segments, the ribosomal protein eS31 simultaneously interacts with Sec-specific transfer RNA (tRNASec) and SBP2, which further stabilizes the assembly. eEFSec is indiscriminate toward L-serine and facilitates its misincorporation at Sec UGA codons. Our results support a fundamentally distinct mechanism of Sec UGA recoding in eukaryotes from that in bacteria.

Automated summary

This study investigated the mechanism of Sec UGA recoding in eukaryotes and found that it is different from the mechanism in bacteria. Cryo-electron microscopy was used to visualize a complex consisting of the noncoding Sec-insertion sequence (SECIS), SECIS-binding protein 2 (SBP2), and the 40S ribosomal subunit, which enables the Sec-specific elongation factor eEFSec to deliver Sec. Additionally, the ribosomal protein eS31 plays a role in connecting the Sec-specific transfer RNA (tRNASec) and SBP2.