This image shows the structure of RNA Polymerase II, an enzyme that transcribes DNA to mRNA. Recent research demonstrates that modified bases within mRNA play a role in regulating gene expression. (Source: NIGMS, Credit: David Bushnell, Ken Westover and Roger Kornberg, Stanford University)
While scientists had hoped that the human genome project would uncover all of humanity’s biological secrets, new findings regarding gene expression continue to make the field of genetics more complex. A team of researchers from the American Friends of Tel Aviv University recently published an article detailing a new component of RNA involved in gene regulation. This discovery presents significant implications in the study of genetic disorders and mutations that can cause diseases such as cancer (1).
Each gene in a eukaryote has a distinct DNA sequence. When the gene is expressed, a molecule known as RNA polymerase transcribes the double stranded DNA into a single-strand of messenger RNA (mRNA). This ensures that the original DNA template remains unchanged. The mRNA is then translated into protein, the basic structural and functional unit that makes up a person’s phenotype, or physical appearance. In gene regulation, certain genes are turned on or off in response to environmental change. As a result, the body can modulate the amount of each protein in order to maintain homeostasis. However, research in gene regulation has focused on the modification of proteins, DNA, or specialized RNA molecules such as small interfering RNAs (siRNA). This new study demonstrates that mRNA likely plays a key regulatory role as well (2).
The team found that a modified RNA base known as m1A occurs frequently at the starting marker, or codon, and that its presence increases translational efficiency, leading to increased synthesis of certain proteins (2). Depriving mammalian cells of glucose or amino acids decreased the abundance of m1A without changing concentrations of other modified RNA bases, such as m6A (2). This suggests that m1A plays a larger role in recording and adjusting the cell’s gene expression in response to environmental stimuli (2).
The researchers suggested several different mechanisms for m1A’s regulatory abilities, which could involve either RNA-RNA interactions or RNA-protein interactions (2). m1A’s positive charge could alter the structure of mRNA, increasing translational efficiency by making some regions of the RNA sequence more accessible to translational binding proteins. m1A could also directly interact with and recruit these binding proteins, facilitating translation (2). Further research is necessary to determine the precise mechanisms that m1A uses to regulate protein synthesis. This research sets the stage for the identification of other possible mRNA regulatory molecules, which can provide insight into diseases that involve abnormal gene expression (1).
References:
1. American Friends of Tel Aviv University. (2016, February 16). New RNA letter regulates gene expression: Discovery brings RNA to the fore of epigenetics. ScienceDaily. Retrieved from sciencedaily.com/releases/2016/02/160216181447.htm
2. Dominissini, D., Nachtergaele, S., Moshitch-Moshkovitz, S., Peer, E., Kol, N., Ben-Haim, M. S., … & Zheng, G. (2016). The dynamic N1-methyladenosine methylome in eukaryotic messenger RNA. Nature. 530, 441-446. doi:10.1038/nature16998