Rapid unleashing of macrophage efferocytic capacity via transcriptional pause release. (https://pubmed.ncbi.nlm.nih.gov/38480883/)

These scientists wanted to understand how macrophages, which are cells in our body that help clean up and get rid of other dead cells, are able to do their job so quickly. They discovered that when macrophages encounter dead cells, they use a special mechanism called transcriptional pause/release to quickly change the way they make certain proteins.

To study this, the scientists looked at the genetic material inside the macrophages and found that a protein called RNA polymerase II plays a key role in this process. By pausing and then releasing this protein during transcription (the process of making proteins from genes), the macrophages were able to respond rapidly to the dead cells they needed to clean up.

The scientists also found that this mechanism was specifically important for the macrophages to clean up dead cells, but not for other tasks like fighting off bacteria or yeast. They identified specific genes and proteins that were controlled by this mechanism, which helped the macrophages efficiently process the dead cells they engulfed.

Additionally, the scientists used special techniques to study how this mechanism works in different types of cells, including zebrafish embryos. They found that when a specific protein called EGR3 was not working properly, the macrophages in the zebrafish had trouble cleaning up dead cells, showing how important this mechanism is for the body to maintain its health.

Overall, this study showed how macrophages use a special mechanism to quickly change how they make proteins when they need to clean up dead cells, helping our bodies stay healthy and functioning properly.

Tufan T., Comertpay G., Villani A., Nelson GM., Terekhova M., Kelley S., Zakharov P., Ellison RM., Shpynov O., Raymond M., Sun J., Chen Y., Bockelmann E., Stremska M., Peterson LW., Boeckaerts L., Goldman SR., Etchegaray JI., Artyomov MN., Peri F., Ravichandran KS. Rapid unleashing of macrophage efferocytic capacity via transcriptional pause release. Nature. 2024 Mar 13. doi: 10.1038/s41586-024-07172-y.