Colliding Ribosomes Activate RNA Repair
Published:26 Jan.2024 Source:Ludwig-Maximilians-Universität München
Crosslinking damage to DNA must be repaired by the cell to prevent premature aging and cancer. However, it was previously unknown whether and how cells sense and resolve crosslinking damage to single-stranded RNA. A team led by Professor Julian Stingele from the Gene Center Munich has now shown that RNA crosslinking damage is toxic because it impairs protein synthesis. The team therefore utilized a new approach to induce and study RNA damage in the absence of DNA damage.
Using this novel experimental system, the researchers uncovered a previously unknown mechanism by which the ribosome can act as a sensor for crosslinking damage. Ribosomes run along the messenger molecule mRNA to translate the information stored in the mRNA into proteins. As the researchers demonstrate, the ribosome gets stuck as soon as it encounters a lesion. This leads to collisions with subsequent ribosomes, triggering removal of the damage. Aldehydes are dangerous because they bind to cellular macromolecules such as DNA, RNA, and proteins, and crosslink them. Crosslinking damage to DNA must be repaired by the cell to prevent premature aging and cancer. However, it was previously unknown whether and how cells sense and resolve crosslinking damage to single-stranded RNA.
A team led by Professor Julian Stingele from the Gene Center Munich has now shown that RNA crosslinking damage is toxic because it impairs protein synthesis. Using this novel experimental system, the researchers uncovered a previously unknown mechanism by which the ribosome can act as a sensor for crosslinking damage. Ribosomes run along the messenger molecule mRNA to translate the information stored in the mRNA into proteins. As the researchers demonstrate, the ribosome gets stuck as soon as it encounters a lesion. This leads to collisions with subsequent ribosomes, triggering removal of the damage.