RNA Epigenetic Mechanism Revealed

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.