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 ferti
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University of Chicago