Journal
SCIENCE
Volume 376, Issue 6599, Pages 1338-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abg3875
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Funding
- Deutsche Forschungsgemeinschaft [SFB740, FOR1805]
- state of Berlin [INST 335/588-1 FUGG, INST 335/589-1 FUGG, INST 335/590-1 FUGG]
- Berlin University Alliance, National Institutes of Health [NIGMS GM097042, GM077073]
- ACS-IL [225752]
- UIC Center for Clinical and Translational Sciences
- North-German Supercomputing Alliance
- NIH [GM129325]
- Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy, and Infectious Diseases
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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.
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.
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