image sulfur modifications transfer RNA1

 

Abstract: 
Sulfur is an essential element in all living organisms. In tRNA molecules, there are many sulfur-containing nucleosides, introduced post-transcriptionally, that function to ensure proper codon recognition or stabilization of tRNA structure. In almost all organisms, 2-thiouridine (s2U) derivatives in the anticodons (position 34) of tRNAs for glutamate, glutamine, and lysine are essential for codon recognition. In several thermophilic bacteria, s2U derivatives at position 54 of all tRNA species enables these organisms to survive at high-temperature. 

The biosynthesis of tRNA sulfur modifications involves unique sulfur-trafficking systems with malutiple ‘sulfur-carrier proteins’ and ‘modification enzymes’ that finally incorporate sulfur atoms into tRNAs. We have discovered the involvement of ubiquitin-related molecules for intermidiate sulfur carrier. Recentry we have demonstrated by spectroscopic (UV-VIS, EPR), biochemical, and structural analyses that Thermus thermophilus TtuA (for s2U 54 synthesis) and MnmA (for s2U 34 synthesis) require oxygen-labile-type iron-sulfur clusters for their activity. The cluster was coordinated by three conserved cysteine residues, and one of the Fe atoms involved directry in sulfur-transfer activity; a quite different mechanism from other 2-thiouridylase subtypes lacking iron-sulfur clusters (MnmA from E. coli and Mtu1 from eukaryotic mitochondria).

We speculated evolutionary scenarios for the sulfur-carrier proteins and sulfurtransferases and concluded that the ubiquitin-like sulfur-carrier proteins and Fe-S cluster-dependent MnmA/TtuA protein are ancient proteins. Our research not only discoverd fundamental ancient and conserved pathways for sulfur utilization but also provides the hints for the development of novel antibiotics: the differences between the essntial s2U thiouridylases of pathogens and humans. 

Speaker: Dr. Naoki Shigi, National Institute of Advanced Industrial Science and Technology (AIST), Japan.

image sulfur modifications transfer RNA2

Speaker bio: 
Dr. Naoki Shigi investigates the essential sulfur metabolism in RNA and its evolutionary scenarios through biochemical and molecular biological approaches especially focusing on the chemistry of  sulfur and oxygen.

Host: Shawn McGlynn, ELSI.

Date: Fri, 19 March, 2021, 15:30-16:30 JST (Fri, 19 March, 06:30-07:30 UTC)

Venue: Online