Sulfur from Within: Cytosolic tRNA Thiouridinylation

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Transfer RNA (tRNA) modifications are crucial for protein synthesis accuracy.
• Thiouridine modifications in tRNA enhance codon recognition.
• The origin and transport of sulfur for these modifications remain incompletely understood.

Purpose of the Study:

• To identify the source of sulfur for cytoplasmic tRNA thiouridine modifications.
• To elucidate the mechanism of sulfur transport from mitochondria to the cytoplasm.
• To determine the specific enzymes involved in supplying sulfur species.

Main Methods:

• Investigated the role of mitochondrial cysteine desulfurase in sulfur metabolism.
• Utilized genetic and biochemical approaches to track sulfur species.
• Examined the function of the mitochondrial transporter Atm1.

Main Results:

• Mitochondrial cysteine desulfurase is the primary source of sulfur for tRNA thiouridine modifications.
• A low-mass sulfur species is exported from mitochondria by the Atm1 transporter.
• This exported sulfur is utilized for thiouridine modification in cytoplasmic tRNAs (tRNA^Lys, tRNA^Glu, tRNA^Gln).

Conclusions:

• Mitochondria play a vital role in supplying essential sulfur for cytoplasmic tRNA modifications.
• The mitochondrial sulfurtransferase system, including cysteine desulfurase and Atm1, is critical for cellular function.
• This pathway highlights the intricate coordination between mitochondrial and cytoplasmic metabolic processes.