AUSTIN, TexasMolecular biologists at The University of Texas at Austin have solved one of the mysteries of how double-stranded RNA is remodeled inside cells in both their normal and disease states. The discovery may have implications for treating cancer and viruses in humans.
The research, which was published this week in Nature, found that DEAD-box proteins, which are ancient enzymes found in all forms of life, function as recycling "nanopistons." They use chemical energy to clamp down and pry open RNA strands, thereby enabling the formation of new structures.
"If you want to couple fuel energy to mechanical work to drive strand separation, this is a very versatile mechanism," said co-author Alan Lambowitz, the Nancy Lee and Perry R. Bass Regents Chair in Molecular Biology in the College of Natural Sciences and Director of the Institute for Cellular and Molecular Biology.
In all cellular organisms RNA (ribonucleic acid) plays a fundamental role in the translation of genetic information into the synthesis of proteins. DEAD-box proteins are the largest family of what are known as " RNA helicases," which unwind RNA.
"It has been known for some time that these enzymes do not function like traditional helicases," said Eckhard Jankowsky, professor of biochemistry at Case Western Reserve University Medical School. "The manuscript now provides the critical information that explains how the unwinding reaction works. It marks a major step towards understanding the molecular mechanics for many steps in RNA biology."
Lambowitz said that the basic insight came when Anna Mallam, a post-doctoral researcher in his lab, hypothesized that DEAD-box proteins function modularly. One area on the protein binds to an ATP molecule, which is the energy source. Another area binds to the double-stranded RNA.
"Once the second domain is latched on to the RNA," said Mallam, "and the first has got its ATP, the 'piston' comes dow
|Contact: Daniel Oppenheimer|
University of Texas at Austin