Featured Research

from universities, journals, and other organizations

New research links common RNA modification to obesity

Date:
October 18, 2011
Source:
University of Chicago
Summary:
Scientists have discovered that a pervasive human RNA modification provides the physiological underpinning of the genetic regulatory process that contributes to obesity and type II diabetes.

Prof. Chuan He has led researchers who have identified a dynamic new cellular pathway, represented here in molecular form, in the genetic regulatory process that contributes to obesity and type II diabetes. The immunofluorescence image at lower center shows individual protein and messenger RNA components in human cells.
Credit: Image courtesy of University of Chicago

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.'"


Story Source:

The above story is based on materials provided by University of Chicago. The original article was written by Steve Koppes. Note: Materials may be edited for content and length.


Journal References:

  1. Guifang Jia, Ye Fu, Xu Zhao, Qing Dai, Guanqun Zheng, Ying Yang, Chengqi Yi, Tomas Lindahl, Tao Pan, Yun-Gui Yang, Chuan He. N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nature Chemical Biology, 2011; DOI: 10.1038/nchembio.687
  2. Chuan He. Grand Challenge Commentary: RNA epigenetics? Nature Chemical Biology, 2010; 6 (12): 863 DOI: 10.1038/nchembio.482

Cite This Page:

University of Chicago. "New research links common RNA modification to obesity." ScienceDaily. ScienceDaily, 18 October 2011. <www.sciencedaily.com/releases/2011/10/111017155622.htm>.
University of Chicago. (2011, October 18). New research links common RNA modification to obesity. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2011/10/111017155622.htm
University of Chicago. "New research links common RNA modification to obesity." ScienceDaily. www.sciencedaily.com/releases/2011/10/111017155622.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
CDC Calls for New Ebola Safety Guidelines

CDC Calls for New Ebola Safety Guidelines

AP (Oct. 20, 2014) Centers for Disease Control and Prevention Director Dr. Tom Frieden laid out new guidelines for health care workers when dealing with the deadly Ebola virus including new precautions when taking off personal protective equipment. (Oct. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins