Chuan He, Ph.D.
University of Chicago
In an NIEHS-funded study, researchers uncovered a previously unknown way that genes code for proteins. Rather than directions going one way from DNA, through messenger RNA (mRNA), to proteins, the study showed that RNA can modify how DNA is transcribed into mRNA and translated to produce proteins.
The researchers studied mice stem cells to explore the mechanisms of gene expression. They found that mRNA modifies how DNA is transcribed using a reversible chemical reaction called methylation, which can change the activity of a DNA segment without changing the sequence. The researchers identified and characterized a number of proteins that recognized the methylated mRNA.
They also discovered that a group of RNAs called chromosome-associated regulatory RNAs (carRNAs) used the same methylation process. However, the carRNAs did not code proteins and were not directly involved in protein translation. Instead, they controlled how DNA was stored and transcribed. The researchers determined that a specific methylation modification known as N6-methyladenosine (m6A) served as a switch to control carRNA levels, which regulated DNA transcription. When they disrupted m6A in mouse stem cells, the abundance of carRNAs increased, as did gene expression.
According to the authors, the findings have major implications in basic biology because they provide a new role for m6A and carRNAs in how DNA becomes proteins, affecting our understanding of mechanisms involved in human disease and drug design.
Citation: Liu J, Dou X, Chen C, Chen C, Liu C, Xu MM, Zhao S, Shen B, Gao Y, Han D, He C. 2020. N 6-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription. Science 367(6477):580–586.