RNA_unzip_1

How protein ‘nanopistons’ unwind RNA

U. TEXAS-AUSTIN (US) — Biologists have discovered how a family of proteins uses chemical energy to clamp down and pry open RNA strands.

The findings help explain how double-stranded RNA is remodeled inside cells—in both normal and disease states—and 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.”

“If you want to couple fuel energy to mechanical work to drive strand separation, this is a very versatile mechanism,” says study co-author Alan Lambowitz, a professor 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,” says Eckhard Jankowsky, professor of biochemistry at Case Western Reserve University Medical School. “The research by Lambowitz and his colleagues now provides the critical information that explains how the unwinding reaction works. It marks a major step toward understanding the molecular mechanics for many steps in RNA biology.”

Lambowitz says that the basic insight came when Anna Mallam, a postdoctoral 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,” Mallam explains, “and the first has got its ATP, the ‘piston’ comes down. It has a sharp edge that drives between the two strands and also grabs on one strand and bends it out of the way.”

Lambowitz, Mallam, and colleagues uncovered this mechanism in Mss116p, a DEAD-box protein in yeast. The mechanism is almost certainly universal to the entire family of the proteins, however, and therefore to all domains of life.

“Every DEAD-box protein that we know about has the same structure,” Lambowitz says, “and they all presumably use the same mechanism.”

This flexibility of DEAD-box proteins is essential to the functioning of healthy cells, which rely on a range of RNA molecules for basic processes, including protein synthesis.

This flexibility is also hijacked in cancers—where over-expression of DEAD-box proteins may help drive uncontrolled cell proliferation—and in infections caused by bacteria, fungi and viruses, which rely on specific DEAD-box proteins for their propagation.

“These findings could have far-reaching implications for our ability to control the activities of proteins in this class when their functions go awry in disease states,” says Michael Bender, program director in the Division of Genetics and Developmental Biology at the National Institutes of Health, which partially funded the work.

Lambowitz even sees potential, much further down the line, for using the nanopistons as the basis of biomedical technology.

“You can even envision, in the far future, how they might be incorporated into artificial nanomachines,” he says, “for switches and other mechanical devices inside and outside the cell.”

Source: University of Texas at Austin

chat3 Comments

You are free to share this article under the Creative Commons Attribution-NoDerivs 3.0 Unported license.

3 Comments

  1. nutrition information fruit

    Pretty section of content. I just stumbled upon your weblog and in accession capital to assert that I
    acquire actually enjoyed account your blog posts. Anyway I’ll be subscribing to your feeds and even I achievement you access consistently fast.

  2. surama

    I will useful websites as well as have my kids check the subsequent commonly. Many thanks! it truly is beneficial to all of us!

  3. gain weight diet

    What’s Taking place i’m new to this, I stumbled upon this I’ve found It positively helpful and it has aided me out loads. I’m hoping to give a contribution & help other users like its
    aided me. Good job.

We respect your privacy.