Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery spotlights key role of mystery RNA modification in cells

07.01.2014
Researchers had known for several decades that a certain chemical modification exists on messenger ribonucleic acid (mRNA), which is essential to the flow of genetic information.

But only recently did experiments at the University of Chicago show that one major function of this modification governs the longevity and decay of RNA, a process critical to the development of healthy cells.

The chemical modification on mRNA in question is called N6-methyladenosine (m6A). A recent study by UChicago scientists reveals how the m6A modification on mRNA could affect the half life of mRNA that in turn regulates cellular protein quantities That discovery could provide fundamental insights into healthy functioning and disorders such as obesity, diabetes, and infertility.

The m6A modification "affects a huge number of messenger RNA in human cells, and yet we did not know its exact function," said Chuan He, professor in chemistry at UChicago and a recently selected investigator of the Howard Hughes Medical Institute. He, Xiao Wang and 11 co-authors from UChicago, University of California, San Diego, and Peking University reported their findings on m6A in the Jan. 2 issue of Nature.

RNA in human cells becomes constantly depleted as it produces proteins, an instability that is essential to biology. "Whenever a cells starts to differentiate, transform into a different type of cell, it needs to express a different set of proteins using a different set of messenger RNA," He said. "It can't be the original set."

The disposal of old RNA allows for the addition of new RNA and the production of different proteins. The Nature study documents that this process is regulated by the insertion or removal of a methyl, a chemical group commonly found in organic compounds.

"Biology is about protein expression regulation: which proteins, how many and at what point," He explained. "If you have the right pattern you get healthy cells. If you get the wrong pattern, you get disease."

It is well known that genetic factors can control protein expression, but the methylation and demethylation of RNA can be epigenetic—operating independent of the sequence of deoxyribonucleic acid (DNA). "This is a very important yet under-explored field," said Wang, the study's lead author and a graduate student in chemistry at UChicago. "It's also a field that is expanding very quickly."

Researchers had long known the presence of the m6A methylation on messenger RNA, but why this occurred remained unknown. He and his associates took a major step in 2011 when they discovered the reverse of the methylation process, demethylation. This discovery involved a so-called "eraser protein" that removed the methyl from RNA, a defect of which leads to obesity. "We basically said, 'Look, if you have certain defect of this function, you get obesity, so there's something going on fundamentally interesting. This methylation appears to play important roles in biological regulation."

He and his associates have now shown that the methylation affects the decay of messenger RNA. "People who are interested in messenger RNA decay or all kinds of cytoplasmic RNA biology now have a new pathway to consider," Wang said.

RNA methylation can vary anywhere from zero to 100 percent as needed to either fine-tune or globally affect protein production. "Researchers had realized that one way to tune the production of protein is to control the lifetime of messenger RNA," Wang said. "We discovered that reversible methylation could be an important parameter in regulating mRNA lifetime."

An extended RNA lifetime would result in more protein production. "If you have a defect of the demethylation mechanism, you could dramatically affect cellular protein levels," He said. And some of those proteins could be essential for energy regulation in the human body, which affects obesity. "Already we know obesity, diabetes and fertility are connected to this, and I'm sure we'll find many other connections."

The demethylases are commonly called erasers. Working alongside eraser proteins are "writer" and "reader" proteins. Writer proteins are the ones that insert methyls into RNA. He's group discovered the first two known eraser proteins since 2011. His group has also identified at least two writer proteins, and many readers, including YTHDF2 that selectively binds m6A in mRNA and controls the mRNA stability as described in their Nature paper.

"YTHDF2 is the first reader protein we have characterized. In fact, it is the first m6A reader protein characterized so far," He said.

Reader proteins endow biological function. "Something has to read a methyl to give it a biological function," He explained. "When you take out the methyl the readers will not read, so there's the regulation. When you put a methyl in, the reader will read." The Nature paper presents the first discovery of a direct link between RNA methylation and biological function, one that tunes the lifetime of mRNA. "Hopefully, I'll have more to report in the future," He said.

Gaining a better understanding of RNA modification may eventually help drug developers devise small molecules that can tune gene expression to kill or control diseased cells, but years of more fundamental research still lies ahead.

"What we have discovered here is a very fundamental biology," He said. "Next we'll look into development, cell differentiation, even neurobiology. This could impact almost every aspect of biology."

Citation: "N6—methyladenosine-dependent regulation of messenger RNA stability," by Xiao Wang, Zhike Lu, Adrian Gomez, Gary C. Hon, Yanan Yue, Dali Han, Ye Fu, Marc Parisien, Qing Dai, Guifang Jia, Bing Ren, Tao Pan and Chuan He, first published online in Nature, Nov. 27, 2013. Published in the print edition on Jan. 2, 2014.

Steve Koppes | EurekAlert!
Further information:
http://www.uchicago.edu

More articles from Life Sciences:

nachricht More detailed analysis of how cells react to stress
08.02.2016 | Universität Zürich

nachricht A new potential biomarker for cancer imaging
05.02.2016 | Universiti Putra Malaysia (UPM)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: From allergens to anodes: Pollen derived battery electrodes

Pollens, the bane of allergy sufferers, could represent a boon for battery makers: Recent research has suggested their potential use as anodes in lithium-ion batteries.

"Our findings have demonstrated that renewable pollens could produce carbon architectures for anode applications in energy storage devices," said Vilas Pol, an...

Im Focus: Automated driving: Steering without limits

OmniSteer project to increase automobiles’ urban maneuverability begins with a € 3.4 million budget

Automobiles increase the mobility of their users. However, their maneuverability is pushed to the limit by cramped inner city conditions. Those who need to...

Im Focus: Microscopy: Nine at one blow

Advance in biomedical imaging: The University of Würzburg's Biocenter has enhanced fluorescence microscopy to label and visualise up to nine different cell structures simultaneously.

Fluorescence microscopy allows researchers to visualise biomolecules in cells. They label the molecules using fluorescent probes, excite them with light and...

Im Focus: NASA's ICESat-2 equipped with unique 3-D manufactured part

NASA's follow-on to the successful ICESat mission will employ a never-before-flown technique for determining the topography of ice sheets and the thickness of sea ice, but that won't be the only first for this mission.

Slated for launch in 2018, NASA's Ice, Cloud and land Elevation Satellite-2 (ICESat-2) also will carry a 3-D printed part made of polyetherketoneketone (PEKK),...

Im Focus: Sinking islands: Does the rise of sea level endanger the Takuu Atoll in the Pacific?

In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister picture is being painted evoking the demise of the island states and their cultures. Are the effects of sea-level rise already noticeable on reef islands? Scientists from the ZMT have now answered this question for the Takuu Atoll, a group of Pacific islands, located northeast of Papua New Guinea.

In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

AKL’16: Experience Laser Technology Live in Europe´s Largest Laser Application Center!

02.02.2016 | Event News

From intelligent knee braces to anti-theft backpacks

26.01.2016 | Event News

DATE 2016 Highlighting Automotive and Secure Systems

26.01.2016 | Event News

 
Latest News

Ocean acidification makes coralline algae less robust

08.02.2016 | Earth Sciences

Online shopping might not be as green as we thought

08.02.2016 | Studies and Analyses

Proteomics and precision medicine

08.02.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>