| RRC ID |
87044
|
| Author |
Mo Y, Ishiguro K, Miyauchi K, Sakaguchi Y, Hanzawa Y, Akiyama N, Murayama A, Machida K, Imataka H, Yamashita A, Ohira T, Shirouzu M, Suzuki T.
|
| Title |
Translational regulation by oxidative desulfuration of tRNA modifications.
|
| Journal |
Nat Commun
|
| Abstract |
Modifications in the anticodon region of transfer RNA (tRNA) are essential for accurate and efficient protein synthesis. 5-Methyl-2-thiouridine derivatives (xm5s2U) are major modifications at the wobble position of tRNA anticodons decoding purine-ending two-codon sets. Although the thiocarbonyl group of xm5s2U enhances decoding efficiency, it is chemically susceptible to oxidative desulfuration, yielding 4-pyrimidinone derivatives (xm5h2U). Here, we identify xm5h2U derivatives in human cells and mouse tissues and confirm their cellular formation by spike-in experiments. Desulfurized tRNAs carrying 5-methoxycarbonylmethyl-4-pyrimidinone (mcm5h2U) show impaired codon recognition in a human reconstituted in vitro translation system. The mcm5h2U modification reduces aminoacylation of tRNAs for lysine, glutamate, and glutamine, but not arginine. Cryogenic electron microscopy reveals the structural basis of altered AAA/AAG decoding by mcm5h2U at the ribosomal A-site. These findings reveal a mechanism by which oxidative desulfuration of tRNA modifications dynamically regulates codon recognition and protein synthesis under oxidative stress conditions in human and mammalian cells.
|
| Volume |
17(1)
|
| Published |
2026-3-10
|
| DOI |
10.1038/s41467-026-70126-7
|
| PII |
10.1038/s41467-026-70126-7
|
| PMID |
41807381
|
| PMC |
PMC12976133
|
| MeSH |
Animals
Anticodon / genetics
Anticodon / metabolism
Codon / genetics
Codon / metabolism
HEK293 Cells
Humans
Mice
Oxidation-Reduction
Oxidative Stress
Protein Biosynthesis*
RNA, Transfer* / chemistry
RNA, Transfer* / genetics
RNA, Transfer* / metabolism
Ribosomes / metabolism
Thiouridine / analogs & derivatives
Thiouridine / chemistry
Thiouridine / metabolism
|
| IF |
12.121
|
| Resource |
| Human and Animal Cells |
MKN45(RCB1001)
HeLa(RCB0007)
293T(RCB2202)
HuH-7(RCB1366) |
