A research team led by Professor Stefan H. Stricker, Professor of Epigenetic Engineering at the Biomedical Center of LMU Munich and group leader at Helmholtz Munich, together with international partners, has developed a new CRISPR-based method that enables the targeted control of protein production in cells. The findings have been published in the journal Science.
The new method, called TAPIR (Targeted Activation of Protein Translation), allows researchers to increase the activity of ribosomal genes and thereby enhance the production of ribosomal RNA (rRNA). This plays a key role in protein synthesis and determines whether cells divide, differentiate, or retain their stem cell properties.
Until now, it has been known that the amount of ribosomal RNA differs between cell types and is altered in numerous diseases. However, it remained unclear whether these changes are the cause or merely a consequence of biological processes. “Our new study shows that targeted activation of rRNA production significantly increases protein synthesis,” explains Stricker, senior author of the publication.
The findings could be particularly relevant for diseases associated with impaired ribosome function. These include ribosomopathies such as Treacher Collins syndrome, a rare congenital disorder that causes craniofacial malformations. In a mouse model, the researchers were able to partially compensate for disease-related changes by specifically stimulating rRNA production.
The research team also observed that similar mechanisms play a role in pancreatic cancer. Tumor cells appear to exploit elevated rRNA production to sustain their rapid growth. In a mouse model of pancreatic cancer, TAPIR increased rRNA production and promoted tumor cell growth. This demonstrates that elevated rRNA production causally contributes to tumor growth rather than merely being a by-product of the disease.
“Our study clearly demonstrates that the regulation of protein biosynthesis plays a central role in both developmental and growth processes as well as in cancer development,” Stricker concludes. He sees TAPIR as a research platform to better understand the role of protein biosynthesis in health and disease and, in the long term, to develop new therapeutic approaches.