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 no
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University of Chicago