A new era in medicine has begun with the development of the first RNA vaccines, which are modified RNAs triggering immune responses in the human immune system. In addition to RNA vaccines, another approach in RNA medicine targets the body’s own RNA and its protein modulators using specifically tailored active substances.

Scientists at the Chemical Genomics Center at the Max Planck Institute of Molecular Physiology in Dortmund have made a significant breakthrough by developing the first small-molecule inhibitors against the RNA-modifying enzyme METTL16. This enzyme is responsible for the regulation of different RNAs and is a promising anti-cancer target.

The newly developed inhibitors prevent the interaction of METTL16 with target RNA, inhibiting the transfer of the methyl group. This groundbreaking research paves the way for a comprehensive investigation of the role of METTL16 in health and disease, bringing us a step closer towards the development of therapeutic agents targeting RNA modifiers. The findings have been published in the journal JACS Au.

While RNA has traditionally been viewed as a passive messenger in the cell, recent discoveries have revealed its multifaceted roles. In addition to transferring genetic information, RNA also controls many cellular processes by regulating gene activity. With more than a dozen identified RNA classes, the cell utilizes RNAi to degrade specific RNA targets to silence genes, particularly in defense against foreign viral DNA.

RNA interacts with a wide array of biomolecules, including other RNAs, DNA, proteins, and metabolites, to form regulatory complexes that control vital cellular processes. Errors in these processes can lead to diseases. The fate of RNA is determined by chemical modifications that affect its stability, structure, interactions, and ultimately its fate.

One of the most abundant RNA modifications is methylation on the N6-position of the RNA-nucleotide adenosine (m6A), which allows the cell to rapidly respond to environmental changes by initiating appropriate cellular responses such as division, differentiation, or migration. Tight control of RNA-methylation is crucial due to its significant impact on cellular functions.