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 Subcutaneous Administration of Multispecific Antibody Makes Tumor Treatment Faster & More Tolerable
01.07.2015 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Why human egg cells don't age well
01.07.2015 | RIKEN

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: X-rays and electrons join forces to map catalytic reactions in real-time

New technique combines electron microscopy and synchrotron X-rays to track chemical reactions under real operating conditions

A new technique pioneered at the U.S. Department of Energy's Brookhaven National Laboratory reveals atomic-scale changes during catalytic reactions in real...

Im Focus: Iron: A biological element?

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and a half billion years ago.

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and...

Im Focus: Thousands of Droplets for Diagnostics

Researchers develop new method enabling DNA molecules to be counted in just 30 minutes

A team of scientists including PhD student Friedrich Schuler from the Laboratory of MEMS Applications at the Department of Microsystems Engineering (IMTEK) of...

Im Focus: Bionic eye clinical trial results show long-term safety, efficacy vision-restoring implant

Patients using Argus II experienced significant improvement in visual function and quality of life

The three-year clinical trial results of the retinal implant popularly known as the "bionic eye," have proven the long-term efficacy, safety and reliability of...

Im Focus: Lasers for Fast Internet in Space – Space Technology from Aachen

On June 23, the second Sentinel mission was launched from the space mission launch center in Kourou. A critical component of Aachen is on board. Researchers at the Fraunhofer Institute for Laser Technology ILT and Tesat-Spacecom have jointly developed the know-how for space-qualified laser components. For the Sentinel mission the diode laser pump module of the Laser Communication Terminal LCT was planned and constructed in Aachen in cooperation with the manufacturer of the LCT, Tesat-Spacecom, and the Ferdinand Braun Institute.

After eight years of preparation, in the early morning of June 23 the time had come: in Kourou in French Guiana, the European Space Agency launched the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

World Conference on Regenerative Medicine: Abstract Submission has been extended to 24 June

16.06.2015 | Event News

MUSE hosting Europe’s largest science communication conference

11.06.2015 | Event News

 
Latest News

Offshore wind park Westermost Rough officially inaugurated

01.07.2015 | Press release

Siemens Velaro train wins "Red Dot" award

01.07.2015 | Awards Funding

Liquids on Fibers - Slipping or Flowing?

01.07.2015 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>