Shared sulfur transfer pathways for Moco biosynthesis and tRNA thiolation

Sulfur is an essential element for all living organisms. The trafficking and delivery of sulfur to the molybdenum cofactor and nucleosides in tRNA is a highly regulated process which proceeds in a complex pathway involving several sulfur transferring proteins. Still numerous open questions remain in connecting the sulfurtransfer for tRNA thiolation and Moco biosynthesis in humans, which we want to study in this project in more detail.

In humans, the cytosolic sulfur modification of mcm5s2U34 in tRNAsLys, Gln, Glu requires the proteins NFS1, TUM1, MOCS3, URM1, CTU1 and CTU2. In contrast, the sulfur insertion for tm5s2U34 modifications in mitochondrial tRNALys, Gln, Glu involves the proteins NFS1, TUM1 and MTU1. Further, for the synthesis of the dithiolene group of Moco, the proteins MOCS2A, MOCS3, TUM1 and NFS1 are involved, a reaction which occurs in the cytosol of humans. Conclusively, Moco biosynthesis and tRNA thiolation are connected in the cytosol and share the same sulfur delivery pathway proteins composed of NFS1, MOCS3 and possibly TUM1.

Our studies will dissect the role of tRNA thiolation and its connection to Moco biosynthesis in human cells in each compartment in detail.