Controlling ribosomal RNA could help researchers target diseases driven by too little or too much protein production.
Cells do not simply make proteins at a fixed pace. They continually adjust production to match their needs, and those changes can help determine whether a cell keeps dividing, adopts a specialized identity, or retains the developmental flexibility of a stem cell. At the center of this process are ribosomes, the molecular machines that build proteins, and the ribosomal RNA that forms their structural and functional core.
Now, researchers led by Professor Stefan H. Stricker of LMU’s Biomedical Center and Helmholtz Munich, working with international collaborators, have shown that ribosomal RNA is more than a passive component of this machinery. Their study, published in Science, provides direct evidence that altering the amount of rRNA can change protein production and influence fundamental processes involved in cell identity, development, and growth.
TAPIR shows rRNA drives protein production
Scientists already knew that cells contain different amounts of ribosomal RNA depending on their type and condition. Abnormal rRNA levels have also been observed in several diseases. The unresolved question was whether those differences actively shaped what cells did or simply appeared after other biological changes had already occurred.
To separate cause from consequence, the researchers needed a way to raise rRNA production deliberately and observe what followed. They developed TAPIR (Targeted Activation of Protein Translation), a CRISPR-based method that increases the activity of ribosomal genes.
Ribosomal genes provide the instructions for producing rRNA, which combines with proteins to form ribosomes. Ribosomes act like molecular assembly lines, reading genetic instructions and building the proteins that cells need to function.
By activating these genes directly, TAPIR allowed the researchers to test whether additional rRNA would change protein output rather than merely accompany it. “Our new study shows that targeted activation of rRNA production significantly increases protein synthesis,” explains Stricker, lead author of the publication.
One mechanism produces opposite disease effects
The researchers next used TAPIR to explore what increased rRNA production might mean in disease. The outcome depended heavily on the biological setting.
One test involved ribosomopathies, a group of disorders caused by impaired ribosome function. These conditions include Treacher-Collins syndrome, a rare congenital disorder associated with facial malformations.
In a mouse model of Treacher-Collins syndrome, targeted stimulation of rRNA production partially compensated for changes linked to the disease. The result suggests that increasing the activity of the protein-making system may help counteract some effects of reduced ribosome function, although the findings remain limited to the model studied.
Pancreatic cancer presented the opposite situation. Cancer cells require large amounts of protein to support their rapid growth, raising the possibility that elevated rRNA production helps tumors maintain that demand.
When the researchers used TAPIR to increase rRNA in a mouse model of pancreatic cancer, the cancer cells grew more rapidly. Because the researchers deliberately raised rRNA levels before observing greater tumor growth, the experiment indicates that increased rRNA production contributes directly to the process rather than appearing only as a consequence of cancer.
Protein production becomes a treatment target
“Our study clearly shows that the regulation of protein biosynthesis plays a key role both in processes of development and growth and in the development of cancer,” says Stricker in summary. He views TAPIR as a research platform for better understanding the impact of protein synthesis on health and disease and for developing new therapeutic approaches over the long term.
The contrasting results reveal why protein production cannot simply be increased or reduced in every disease. Raising rRNA activity might prove useful when ribosome function is insufficient, but the same intervention could support tumors that already depend on unusually high protein output.
TAPIR gives researchers a way to investigate those differences directly. Future work could examine whether carefully controlling rRNA production might help treat disorders caused by weakened ribosome function or identify new therapeutic targets in cancers where protein production has become excessive.
Reference: “Manipulation of protein translation and stem cell self-renewal by CRISPR activation of rRNA transcription” by Maximilian Wiesbeck, Emilie L. Alard, Florencia Merino, Niti Chowdhury, Luisa Egert, Anna Danese, Simon Imhof, Matilde Iraci Borgia, Akshaya Rajan, Nadine Fernandez-Novel Marx, Edina Kepesidis, Anna Köferle, Luis Miguel Cerron-Alvan, Franziska Vierl, Thi-Tram Truong, Manja Thorwirth, Lorina Bilalli, Jovica Ninkovic, Rico Schieweck, Markus Diefenbacher, Stefanie M. Hauck, Paul Trainor, Faraz K. Mardakheh, Magdalena Götz and Stefan H. Stricker, 2 July 2026, Science.
DOI: 10.1126/science.aeh1348
Never miss a breakthrough: Join the SciTechDaily newsletter.
Follow us on Google and Google News.