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

Hilal, Tarek; Killam, Benjamin Y; Grozdanović, Milica; Dobosz-Bartoszek, Malgorzata; Loerke, Justus; Bürger, Jörg; Mielke, Thorsten; Copeland, Paul R et al. · Science · 2022

basic_science · Level V

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Abstract

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 40<i>S</i> 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 (tRNA<sup>Sec</sup>) 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.

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