Mystery m6A Modification of mRNA Governs Half-Life of Molecule

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 U. Chicago scientists and collaborators 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 RNAs in human cells, and yet we did not know its exact function," said Dr. Chuan He, professor in chemistry at U. Chicago and a recently selected investigator of the Howard Hughes Medical Institute. He, Xiao Wang and 11 co-authors from U. Chicago, University of California, San Diego, and Peking University reported their findings on m6A in the January 2, 2014 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," Dr. 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 group, a chemical group commonly found in organic compounds.
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