New CRISPR Tool Gives Scientists Control Over Cellular Protein Production

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 [...]

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