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Updated: Dec 15, 2025

DNA-Tethered RNA Polymerase for Programmable In vitro Transcription and Molecular Computation
Published on: December 29, 2021
Structure-based mechanistic insights into catalysis by tRNA thiolation enzymes
Ornella Bimai1, Simon Arragain1, Béatrice Golinelli-Pimpaneau1
1Laboratoire de Chimie des Processus Biologiques, UMR 8229 CNRS, Collège de France, Université Paris Sciences et Lettres, 11 Place Marcelin Berthelot, 75231 Paris cedex 05, France.
This review details tRNA thiolation enzymes, which add sulfur to RNA nucleosides for accurate protein synthesis. It explores two key mechanisms involving persulfide or [4Fe-4S] cluster sulfur transfer.
Area of Science:
- Biochemistry
- Molecular Biology
- RNA Biology
Background:
- Ribonucleic acid (RNA) undergoes post-transcriptional modifications, including sulfur additions to nucleosides.
- Sulfur-containing nucleosides like 2-thiouridine (s²U) and 2-methylthioadenosine (ms²A) in transfer RNAs (tRNAs) are crucial for accurate genetic translation.
- These modifications ensure fidelity in protein synthesis from messenger RNA (mRNA).
Purpose of the Study:
- To review recent advancements in understanding the mechanisms and structures of tRNA thiolation enzymes.
- To elucidate the catalytic processes involved in the non-redox substitution of oxygen with sulfur in nucleosides.
- To highlight the structural and mechanistic diversity of enzymes responsible for tRNA sulfur modifications.
Main Methods:
- Mechanistic studies of tRNA thiolation enzymes.
- Structural characterization of enzyme-substrate interactions.
- Biochemical assays to investigate sulfur transfer pathways.
Main Results:
- Two distinct catalytic mechanisms for tRNA thiolation have been identified.
- Mechanism 1: Sulfur transfer via persulfide formation on catalytic cysteine residues.
- Mechanism 2: Sulfur transfer mediated by a [4Fe-4S] cluster coordinated by three conserved cysteines.
Conclusions:
- tRNA thiolation enzymes employ diverse strategies to incorporate sulfur into RNA nucleosides.
- Understanding these mechanisms provides insight into the regulation of translation and genetic code accuracy.
- Further research into these enzymes could reveal novel therapeutic targets for diseases related to translation errors.
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