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Biological Chemistry

RNA Epigenetic Mechanism Revealed

m6A modification induces RNA shape change that promotes protein binding

by Stu Borman
March 2, 2015 | A version of this story appeared in Volume 93, Issue 9

The biological effects of epigenetic changes to genomic DNA, such as methylation and histone modification, have been widely studied. Similar changes to mRNAs also affect biological processes but are not yet as well understood. The most common epigenetic modification to RNA is the methylation of adenosine nucleotides to form N6-methyladenosine (m6A) groups. Researchers now report one way this modification works—by changing the conformation of mRNA in a manner that allows an RNA-binding protein called HNRNPC to bind with higher affinity. The work was carried out by Marc Parisien, now at McGill University; Tao Pan at the University of Chicago; and coworkers (Nature 2015, DOI: 10.1038/nature14234). They show that when m6A binds to one site on folded mRNA, a five-uridine sequence opposite the binding site changes shape. The shape change helps HNRNPC bind more avidly—an interaction that has major effects on mRNA function. They found more than 39,000 mRNAs in which this m6A switching action occurs. “Besides HNRNPC, m6A-switches may regulate the function of many other RNA-binding proteins,” the researchers predict.

Binding of m6A to mRNA causes a change in conformation that allows proteins like HNRNPC to bind with higher affinity, an interaction that modifies mRNA abundance and splicing.
Credit: Nature
Binding of m6A to mRNA causes a conformation change that promotes HNRNPC binding and affects mRNA function.


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