Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Rehydrate -- your RNA needs it

25.08.2006
Water, that molecule-of-all-trades, is famous for its roles in shaping the Earth, sustaining living creatures and serving as a universal solvent.

Now, researchers at the University of Michigan and the Academy of Sciences of the Czech Republic have uncovered two previously unknown roles for water in RNA enzymes, molecules which themselves play critical roles in living cells and show promising medical applications.

The researchers' findings will be published online in the Proceedings of the National Academy of Sciences (PNAS) this week.

RNA enzymes, also known as ribozymes, accelerate chemical reactions inside cells, just as their better-known protein counterparts do. And just as a protein enzyme is not a static structure, a ribozyme also changes shape, cycling back and forth between active and inactive forms (called conformations).

In earlier work, a team led by U-M's Nils Walter, associate professor of chemistry, found that modifications made anywhere on the ribozyme molecule---even far from the site where the chemical reaction occurs---affect the rates at which the enzyme changes conformation and catalyzes the reaction. Something similar had been seen in protein enzymes, but never before in RNA enzymes.

The earlier finding, published in PNAS two years ago, suggested that information about changes in distant parts of the ribozyme travels through some sort of network to the core of the molecule, where chemical reactions take place. The latest work shows that water molecules trapped inside the ribozyme's core are essential components of that network.

The network acts like a jostling crowd at a cocktail party, where hydrogen bonds---weak, electrostatic attractions between molecules or parts of molecules---take the place of handshakes. Water molecules trapped in ribozymes can form hydrogen bonds with other water molecules or with parts of the ribozyme molecule.

"The way we interpret the data is that in ribozymes, a chemical modification introduced at one place changes the local structure slightly," Walter said. The building blocks making up the ribozyme wiggle into different positions and in the process must let go of some hydrogen bonds and form others, just as partygoers shift position and engage with other guests.

"As a consequence, their hydrogen bonding partners---some of which are water molecules---also rearrange. Then their hydrogen bonding partners also rearrange, creating a domino effect, where a local modification spreads throughout the molecule and modifies the structure elsewhere, even at quite a distance," Walter said. Water facilitates the process by increasing the number of hydrogen bonds and making the ribozyme behave as an interconnected whole.

Walter and coworkers also found evidence that water is directly involved in catalyzing reactions in the ribozyme's core, another previously unknown role. The research team explored the new roles of water molecules using a combination of computational simulations and a technique called single-molecule fluorescence resonance energy transfer (FRET), which allowed the researchers to directly observe and measure how quickly the ribozyme switched forms and how the rates changed when various parts of the molecule were altered.

The situation in ribozymes contrasts with what happens in protein enzymes, which repel water from their cores and rely on direct contact, rather than a network of hydrogen bonds, to communicate structural changes from one part of the molecule to another.

So far, the researchers have focused on one particular ribozyme, but Walter predicts the findings will apply to other RNAs. If so, those findings should be of great interest to scientists who are learning more all the time about the diverse roles of RNA. Once thought to be only a passive carrier of encoded genetic information, RNA is now known to regulate gene expression and other important cellular processes and to act as a sort of sensor---detecting cellular signals and carrying out appropriate reactions in response. In fact, there are many more so-called non-protein coding RNAs in the cell (around 100,000 in humans), which are not translated into protein, than there are protein coding messenger RNAs (about 25,000), making these vast numbers of RNA molecules central players in our bodies.

Work is also underway in academic and industrial labs around the world to engineer RNA for medical purposes. The engineered molecules, called RNA aptamers, are selected for their ability to bind to particular proteins involved in certain diseases, blocking key steps in the disease process.

"It's likely that water helps mediate the binding between these aptamers and their disease-causing protein targets, ultimately keeping the protein away from where it can wreak havoc," Walter said. "So the fundamental understanding we are gaining of the role of water in RNA almost certainly will have relevance in the treatment or prevention of disease."

Nancy Ross-Flanigan | EurekAlert!
Further information:
http://www.umich.edu

More articles from Life Sciences:

nachricht Closing the carbon loop
08.12.2016 | University of Pittsburgh

nachricht Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Closing the carbon loop

08.12.2016 | Life Sciences

Applicability of dynamic facilitation theory to binary hard disk systems

08.12.2016 | Physics and Astronomy

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D

08.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>