Solving A Protein Mystery

For 20 years, researchers have known that the speed of protein synthesis on the ribosome of bacteria matches that of mRNA production, but how the cell keeps these two components of protein production moving to the same beat has been a mystery.

Now, a duo of papers reveals the mechanism and kinetics that couple transcription and translation in bacteria. The findings reverse a long-standing assumption that RNA polymerase, which transcribes DNA into mRNA, sets the pace of the coupling. Instead the ribosome directs the speed of the transcription-translation relationship, the studies show. The findings may also provide a new bacterial target for the development of antibiotics.

A team of researchers led by Paul Rösch, a protein chemist at the University of Bayreuth, in Germany, used nuclear magnetic resonance spectroscopy to find “the missing link” between transcription by RNA polymerase and translation by the ribosome. The link involves the binding of a ribosomal protein called NusE to a protein called NusG, which can simultaneously attach to the transcription machinery, they report in Science (2010, 328, 501).

“The coupling of transcription and translation has been known for a very long time, but the breakthrough here is the direct physical link between the two,” comments Robert Landick, a biochemist at the University of Wisconsin, Madison, who studies bacterial transcription. “What has never been understood until now is that the ribosome is actually moving with a physical connection to RNA polymerase.”

Interfering with the linkage between NusE and NusG “could be a new way to interfere with bacterial gene expression and serve as a new target for antimicrobial therapy,” notes Evgeny Nudler, a biochemist at the New York University School of Medicine.

Nudler led the team of researchers who figured out the kinetics of transcription and translation coupling, also published in the current issue of Science (2010, 328, 504).

They found that when the ribosome binds to mRNA and starts churning out protein, this in turn propels RNA polymerase to increase the speed of mRNA synthesis. When bacteria are treated with an antibiotic that seizes the ribosome, or when bacteria are engineered to produce faulty ribosomal proteins, RNA polymerase slows down—and sometimes stops altogether—to compensate.

Although the physical coupling of transcription and translation happens in bacterial cells, it is unlikely to occur in human cells (or any eukaryotic cells), because RNA polymerase and the ribosome work in separate compartments of eukaryotic cells, Landick says. However, researchers have found glimpses of an analogous coupling in eukaryotic cells, he adds, between transcription and the spliceosome, which is responsible for deleting unnecessary sequences in the mRNA of higher organisms.

Chemical & Engineering News

ISSN 0009-2347

Copyright © 2011 American Chemical Society