Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New research links common RNA modification to obesity

18.10.2011
An international research team has discovered that a pervasive human RNA modification provides the physiological underpinning of the genetic regulatory process that contributes to obesity and type II diabetes.

European researchers showed in 2007 that the FTO gene was the major gene associated with obesity and type II diabetes, but the details of its physiological and cellular functioning remained unknown.

Now, a team led by University of Chicago chemistry professor Chuan He has demonstrated experimentally the importance of a reversible RNA modification process mediated by the FTO protein upon biological regulation. He and 10 co-authors from Chicago, China and England published the details of their finding in the Oct. 16 advance online edition of Nature Chemical Biology.

He and his colleagues have shown, for the first time, the existence of the reversible RNA modification process — called methylation — and that it potentially impacts protein expression and function through its action on a common RNA base: adenosine. The process is reversible because it can involve the addition or removal of a methyl group from adenosine. The team found that the FTO protein mediates cellular removal of the methyl group.

"An improved understanding of the normal functions of FTO, as exemplified by this work, could aid the development of novel anti-obesity therapies," said Stephen O'Rahilly, professor of clinical biochemistry and director of the Metabolic Research Laboratories at the University of Cambridge. O'Rahilly, a leading researcher in obesity and metabolic disease who also has studied FTO, was not directly involved in He's project.

"Variants around the FTO gene have consistently been associated with human obesity and artificial manipulation of the fto gene in mice clearly demonstrates that FTO plays a crucial role in the regulation of body weight," O'Rahilly explained. "However, the development of a deeper understanding of the normal biological role of FTO has been challenging."

Scientists already had demonstrated that FTO removes methyl groups from nucleic acids, but only on one rare type of DNA or RNA methylation. The new research from He and his colleagues shows that FTO also acts on the common messenger RNA modification called N6-methyladenosine, O'Rahilly said.

The paper arose from He's investigations of the AlkB family of proteins that act on nucleic acids. Based on this work, He and his collaborators proved that human cells exhibit reversible methylation of RNA bases, which significantly impact critical life processes.

Important but mysterious

Every human messenger RNA carries on average three to six methylations on adenosine. Scientists knew these methylations were extremely important but their function remained a mystery, He said. "For the first time, we show that these methylations are reversible and play a key role in human energy homeostasis," the process by which the body maintains a complex biochemical dynamic equilibrium.

The modification of N6-methyladenosine in messenger RNA is pervasive throughout the mammal kingdom and many other organisms. Despite its abundance, this modification's exact functional role remains unknown, He said. But his team's discovery strongly indicates that the modification has major roles in messenger RNA metabolism.

The finding may open a new research field — RNA epigenetics — for delving into the realm of biological regulatory processes, He said. The epigenetics of DNA and histones (proteins that package DNA in human cells) have become well-explored topics on the frontiers of biological research over the last 10 to 20 years. "It is safe to say 50 percent of biologists work on subjects related to epigenetics one way or another," He said.

DNA (deoxyribonucleic acid) for decades has reigned as king over biological research on epigenetics of nucleic acids, as He noted in the December 2010 issue of Nature Chemical Biology. RNA (ribonucleic acid) modification was regarded more as a vassal that merely fine-tunes gene expression and regulation, until this recent discovery, which confirms the speculation by He and others that RNA modification has secretly wielded a far greater genetic influence than anyone had previously suspected. That's why, as He wrote last year, "reversible RNA modification might represent another realm for biological regulation in the form of 'RNA epigenetics.'"

Citations: "N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO," by Guifang Jia, Ye Fu, Xu Zhao, Qing Dai, Guanqun Zheng, Ying Yang, Chengqi Yi, Tomas Lindahl, Tao Pan, Yun-Gui Yang and Chuan He, Nature Chemical Biology, advance online publication Oct. 16, 2011.

"RNA epigenetics?" by Chuan He, Nature Chemical Biology, Dec. 2010.

Funding: National Institutes of Health, Chinese Academy of Sciences, Chicago Biomedical Consortium, Beijing Institute of Genomics.

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

More articles from Life Sciences:

nachricht Tag it EASI – a new method for accurate protein analysis
19.06.2018 | Max-Planck-Institut für Biochemie

nachricht How to track and trace a protein: Nanosensors monitor intracellular deliveries
19.06.2018 | 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: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

Im Focus: Photoexcited graphene puzzle solved

A boost for graphene-based light detectors

Light detection and control lies at the heart of many modern device applications, such as smartphone cameras. Using graphene as a light-sensitive material for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Carbon nanotube optics provide optical-based quantum cryptography and quantum computing

19.06.2018 | Physics and Astronomy

How to track and trace a protein: Nanosensors monitor intracellular deliveries

19.06.2018 | Life Sciences

New material for splitting water

19.06.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>