Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mechanism of RNA recoding: New twists in brain protein production

17.03.2005


RNA loops and knots guide genetic modifications



University of Connecticut Health Center scientist, Robert Reenan, has uncovered new rules of RNA recoding--a genetic editing method cells use to expand the number of proteins assembled from a single DNA code. According to his work, the shape a particular RNA adopts solely determines how editing enzymes modify the information molecule inside cells. The study may help explain the remarkable adaptability and evolution of animal nervous systems--including the human brain. The work appears in the March 17 issue of Nature.

DNA sequences spell out the instructions for making protein but they aren’t always followed to the letter. Sometimes, the genetic recipe gets edited after cells copy DNA to RNA--a close chemical relative--during transcription. Think of DNA as an unalterable "read only" copy of the genetic code and the RNA as a "writable" working copy that cells can edit extensively--adding, deleting, and modifying the molecular letters and words that guide protein assembly. Often, even simple editing such as changing one letter in an RNA molecule affects the resulting protein’s function. There are many different types of RNA editing.


Reenan’s group studies one particular method called A-to-I RNA recoding. It occurs when an enzyme chemically "retypes" RNA letters at specific locations, changing adenosine (A) to inosine (I). Proteins responsible for fast chemical and electrical signaling in animal nervous systems are the main targets of this process. In a prior study, Reenan’s group identified species-specific patterns of RNA recoding on such targets, but didn’t explain how they were determined or how they may have evolved. His new study does both.

By comparing the same highly edited RNA from over 30 insects, Reenan uncovered some general rules of A-to-I recoding. He observed that the RNA of different insects folds into unique structures. These shapes single-handedly determine the species-specific RNA editing patterns that Reenan previously observed. For example, part of the RNA molecule he focused on--the code for the protein synaptotagmin, a key player in neuronal chemical signaling--looks like a knot in fruit flies, but a loop in butterflies. These molecular knots and loops bring regulatory regions of the RNA together with sites destined for recoding, guiding editing enzymes to act there. As proof, Reenan coaxed fruit fly RNA to adopt a "mosquito-like" structure by making small changes in the molecule--a procedure he dubbed "guided evolution." Predictably, cells edited the reconfigured fly RNA in the mosquito-like pattern.

In all species Reenan studied, the RNA region that regulates folding is located within an intron--a string of non-protein coding letters that cells cut out or "splice" from the molecule during processing. RNA recoding can’t occur without introns, so cells must have a way of slowing down splicing long enough for editing enzymes to do their job. "The structures imply a really strong interaction between splicing and editing," according to Reenan, who notes that, "these complicated structures actually tie up--literally--splicing signals." By making small alterations in introns during evolution, different insects conserved the basic RNA code for making important proteins, but developed a way to tweak the resulting nerve cell protein’s function in a species-specific manner. The species-specific editing may give insects different abilities by modifying behaviors.

According to Joanne Tornow, the National Science Foundation program manager who oversees Reenan’s work, "These findings provide dramatic evidence that intron sequences, which were once thought to serve little purpose of their own, are functionally important in the accurate expression and regulation of these genes. What’s more," she adds, "this work is revealing a new type of genetic code, which incorporates both sequence and structural signals." She anticipates this work, also funded in part by the National Institutes of Health, will "greatly increase our ability to interpret the information encoded in the genome."

Researchers still don’t know why editing occurs, but posit that organisms use it to increase protein variety. RNA recoding lets cells generate an array of proteins from a single DNA sequence, each with a slightly different function. Producing different proteins in a cell at once could let organisms fine tune biological processes with extreme precision--a level of flexibility the DNA code doesn’t afford. "Genetics is digital," says Reenan, adding "Editing changes digital to analog," letting cells "dial up" the exact amounts of altered proteins required at any given time or place.

No matter why organisms do it, one thing is clear--serious problems can occur when RNA editing goes awry. RNA recoding defects cause neurological problems in all of the animals examined to date.

Nicole Mahoney | EurekAlert!
Further information:
http://www.nsf.gov

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

DGIST develops 20 times faster biosensor

24.04.2017 | Physics and Astronomy

Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging

24.04.2017 | Materials Sciences

Atomic-level motion may drive bacteria's ability to evade immune system defenses

24.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>