New Function For tRNA

New findings indicate that transfer RNA (tRNA) has another function in addition to its long-established role in gene expression. tRNA also helps control apoptosis, or programmed cell death, according to a team of researchers led by University of Pennsylvania cancer biologist Xiaolu Yang (Mol. Cell 2010, 37, 668).

During gene expression, DNA is first transcribed into messenger RNA. Next, tRNA molecules—each carrying an amino acid as cargo—bind to successive nucleotides in the messenger RNA. A ribosome links these amino acids together to form a protein, and the unloaded tRNAs are subsequently released.

Now, “for the first time, we show that tRNA has a clear role beyond the transmission of genetic information,” Yang says. “It actually blocks apoptosis.”

Apoptosis eliminates unwanted, damaged, or harmful cells. It can be triggered by signals from either inside or outside a cell. Internal signals, such as DNA damage, prompt the cell’s power generators, or mitochondria, to release cytochrome c into the intracellular fluid, known as the cytosol. Mitochondria normally use cytochrome c to produce adenosine triphosphate, which powers metabolism. But when it’s released into the cytosol, cytochrome c instead binds to the protein Apaf-1, which activates caspases that cleave various cellular proteins, ultimately killing the cell.

Yang, along with Yide Mei, Jeongsik Yong, and other colleagues, have discovered that tRNA also binds to cytochrome c, stopping it from binding to Apaf-1 and thereby preventing apoptosis.

The researchers have “unveiled a completely unexpected level of control in the apoptotic process,” comment Bram J. van Raam and Guy S. Salvesen, who study apoptosis and cell death at Sanford-Burnham Medical Research Institute, in La Jolla, Calif. (Mol. Cell 2010, 37, 591). Raam and Salvesen suggest the findings also “might indicate a new and important level of nuclear control over mitochondrial metabolism.”

tRNA is highly expressed in tumor cells. It inhibits apoptosis in these cells, Yang believes, and could thus be targeted for tumor therapy.