New Insights Into m6A Modifications Could Aid Cancer Treatments

A team at the University of Würzburg (JMU) in Germany has identified a highly efficient process that breaks down messenger RNA (mRNA) molecules in human cells. This discovery provides insights into a key RNA modification, N6-methyladenosine (m6A), which is linked to numerous biological processes and diseases, including cancer.

The role of mRNA and modifications in protein synthesis

Messenger RNAs act as blueprints for proteins in cells, guiding ribosomes to produce proteins essential for cell function and survival. To regulate protein production, mRNAs undergo modifications that serve as additional instructions, ensuring proteins are synthesized in the right quantities and at the right times. One such modification, m6A, plays a crucial role in marking mRNA for degradation after the necessary proteins have been made.

Faster, targeted mRNA degradation

The Würzburg researchers were the first to observe a degradation process directly coupled to protein production. This mechanism relies on m6A being positioned in specific regions of the mRNA, allowing efficient breakdown of the molecule. This precise targeting is crucial for proteins involved in cell differentiation – determining whether a cell becomes a nerve, muscle or skin cell.

Unlike previously identified pathways, this process is significantly faster and more effective, providing the cell with a way to tightly control protein levels. This is vital because overproduction of certain proteins can disrupt cellular balance and lead to harmful outcomes.

Clinical potential of m6A-targeting drugs

The findings could guide the development of therapies that control m6A modification to regulate protein production. For instance, by suppressing m6A in specific mRNAs, drugs might promote the production of beneficial proteins. Conversely, enhancing m6A modification could prevent the production of harmful proteins.

However, until now, scientists struggled to predict how such drugs would behave due to limited understanding of where m6A modifications needed to be located to trigger degradation. This research offers new insights into the relationship between m6A placement and mRNA sensitivity, improving the precision of drug development targeting these pathways.

Future directions

The team plans to explore the details of how ribosomes detect m6A modifications and how this knowledge can be applied clinically. Further investigations could unlock therapeutic strategies for conditions such as cancer and metabolic disorders, where m6A activity is often disrupted.

Reference: Zhou Y, Ćorović M, Hoch-Kraft P, et al. m6A sites in the coding region trigger translation-dependent mRNA decay. Mol Cell. 2024;84(23):4576-4593.e12. doi: 10.1016/j.molcel.2024.10.033

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