Study reveals cellular quality control

Cells pay even closer attention to quality control of genetic information than scientists previously thought, according to new findings by UW Medical School researchers. Before sending genetic molecules out of the nucleus to sites where they will ultimately function, cells check to see that they are complete and ready to go.

“With this finding, we can start to think of the nuclear envelope as more than a shell that keeps the components of the nucleus together,” said UW Medical School Professor of Biomolecular Chemistry James Dahlberg. “We now know it’s also a barrier that makes sure genetic material isn’t exported prematurely from the nucleus, which could be disastrous for the cell.”

Dahlberg, a member of the National Academy of Sciences, and Elsebet Lund, a senior scientist in the department of biomolecular chemistry, report their findings in the Dec. 11 issue of the journal Science.

Proteins, essential for all life processes, are made up of building blocks of amino acids arranged in specific sequences determined by genetic instructions. The machinery that builds the proteins involves a special molecule called transfer RNA (tRNA), which delivers the amino acids to protein-assembly factories known as ribosomes.

After several years of studying mechanisms by which molecules are transported in and out of the nucleus, Dahlberg and Lund recently asked how cells determine exactly when tRNA is able to function. In their experiments, they showed that each tRNA must be able to attach its amino acid before it is exported from the nucleus.

“Like a last-minute quality-control check on the loading dock, this system may be the way the cell says, ‘Yes, you’re ready to be sent out to the ribosome,'” he said.

The quality-control process, known as proofreading, works in many areas of biology, but was never known to occur in tRNA export until the UW experiments.

In their studies, the researchers first made the unexpected discovery that amino acids can attach to tRNA in the nucleus, not just outside it in the cytoplasm. They then showed that amino acid attachment is required for efficient delivery of the tRNA out of the nucleus.

“This told us the cell really does monitor whether the tRNA can function before it is released into the cytoplasm,” he said.

Dahlberg said it behooves cells to ensure tRNA molecules don’t leave the nucleus before they’re fully matured with amino acids attached. He noted that once they’re out, there’s no way back for further maturation.

“Immature tRNA can cause a big mess in protein assembly,” he said.