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

More articles from Life Sciences:

nachricht What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

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

Simple processing technique could cut cost of organic PV and wearable electronics

06.12.2016 | Materials Sciences

3-D printed kidney phantoms aid nuclear medicine dosing calibration

06.12.2016 | Medical Engineering

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>