Navigation Links
Discovery spotlights key role of mystery RNA modification in cells
Date:1/6/2014

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 epigeneticoperating 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."


'/>"/>

Contact: Steve Koppes
skoppes@uchicago.edu
773-702-8366
University of Chicago
Source:Eurekalert  

Related biology news :

1. Genetic discovery points the way to much bigger yields in tomato, other flowering food plants
2. Rheumatoid arthritis research shows the potential of large-scale genetic studies for drug discovery
3. Life Sciences Discovery Fund announces R&D grants
4. Chicago scientist involved in discovery of 4 new mammal species in Democratic Republic of Congo
5. U-M tinnitus discovery opens door to possible new treatment avenues
6. New discovery on how skin cells form bridges paves the way for advances in wound healing
7. Environment drives genetics in Evolution Canyon; discovery sheds light on climate change
8. CNIO study chosen as discovery of the year in regenerative medicine
9. Canadian researchers lead groundbreaking discovery in deadly childhood cancer
10. Surprising discovery: The skin communicates with the liver
11. Discovery of partial skeleton suggests ruggedly built, tree-climbing human ancestor
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Discovery spotlights key role of mystery RNA modification in cells
(Date:3/29/2016)... 29, 2016 LegacyXChange, Inc. (OTC: ... and SelectaDNA/CSI Protect are pleased to announce our successful ... a variety of writing instruments, ensuring athletes signatures against ... collectibles from athletes on LegacyXChange will be assured of ... DNA. Bill Bollander , CEO states, ...
(Date:3/22/2016)... , March 22, 2016 ... research report "Electronic Sensors Market for Consumer Industry by ... & Others), Application (Communication & IT, Entertainment, ... - Global Forecast to 2022", published by ... is expected to reach USD 26.76 Billion ...
(Date:3/21/2016)... , March 22, 2016 ... with passcodes for superior security   ... leading provider of secure digital communications services, today announced ... technology and offer enterprise customers, particularly those in the ... recognition and voice authentication within a mobile app, alongside, ...
Breaking Biology News(10 mins):
(Date:5/4/2016)... WHIPPANY, N.J. , May 4, 2016 /PRNewswire/ ... evaluating its oncology compound Stivarga ® (regorafenib) ... hepatocellular carcinoma (HCC) has met its primary endpoint ... The study, called RESORCE, evaluated the efficacy and ... disease has progressed after treatment with sorafenib. The ...
(Date:5/4/2016)... May 4, 2016 According to ... "Metabolomics Market - Global Industry Analysis, Size, Share, Growth, ... is anticipated to expand at a CAGR of 17.1% ... by 2024. Metabolomics is the extensive study ... biofluids, tissues or organisms. Together, these small molecules and ...
(Date:5/4/2016)... NY (PRWEB) , ... May 04, 2016 , ... ... leveraged recent innovations in biotechnology to help treat hormonal and stress related hair ... Nutrafol® has captured the hearts of key opinion leaders in the medical and ...
(Date:5/3/2016)... ... May 03, 2016 , ... ... development, skill-building and compliance training platform on mobile devices, today released a new ... Regulatory Requirements for Medical Devices. The course is essential for owners or operators ...
Breaking Biology Technology: