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

Science. 2022 Jun 17;376(6599):1338-1343. doi: 10.1126/science.abg3875. Epub 2022 Jun 16.


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.

MeSH terms

  • Codon, Terminator* / genetics
  • Cryoelectron Microscopy
  • Humans
  • Peptide Chain Elongation, Translational* / genetics
  • Protein Conformation
  • RNA-Binding Proteins* / chemistry
  • RNA-Binding Proteins* / genetics
  • Ribosomes* / chemistry
  • Selenocysteine* / chemistry
  • Selenocysteine* / genetics
  • Selenocysteine* / metabolism
  • Selenoproteins* / biosynthesis
  • Selenoproteins* / genetics


  • Codon, Terminator
  • RNA-Binding Proteins
  • SECISBP2 protein, human
  • Selenoproteins
  • Selenocysteine