Scripps Confirms QC Mechanism that Protects Protein Production

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Scientists at Scripps’ Florida campus showed for the first time that quality control steps exist in the production of proteins, which presents a target for anti-cancer drug development.

On Sep. 7, 2017, The Scripps Research Institute (TSRI), a not-for-profit organization focused on research in biomedical sciences, published online a study from scientists at its Florida campus that showed for the first time that quality control (QC) steps exist in the assembly of cellular factories that produce proteins, the basic working units of any cell. The study was led by Katrin Karbstein, an associate professor in the Department of Integrative Structural and Computational Biology.

The production of proteins is a complex process, made up of a series of smaller intricate biochemical steps that succeed because of an equally complex number of quality controls. Without them, the process would irreparably break down and diseases like cancer would run rampant, according to TSRI.

“With important cellular machines like ribosomes, it makes sense that mechanisms exist to make sure things work correctly,” Ms. Karbstein said in the institute’s press release. “We’ve confirmed for the first time that such a quality control function exists for these small ribosomal subunits that, in essence, do a test run but don’t produce a protein-without it, mistakes in RNA translation would produce dangerous mutated proteins.”

Ribosomes, large macromolecular machines required for cell growth in all organisms, catalyze the production of proteins in all cells. They read the genetic code carried by messenger RNA (mRNA) and catalyze or translate that code into proteins within cells, assembling them from amino acids.

Understanding the process of ribosome assembly is an important area of research because ribosome assembly is critical for cell growth. This process involves almost 200 essential proteins known as "assembly factors" in addition to the four RNA molecules and 78 ribosomal proteins that are part of a mature ribosome.

“We used genetic and biochemical experiments to show that bypassing this step in translation-like cycle produces defects,” said Homa Ghalei, the first author of the study, in the institute’s press release. “Our results show that this cycle is a quality control mechanism that ensures the fidelity of the cellular ribosome pool.”


QC Steps Link to Anti-Cancer Drug Development

The link between defects in ribosome assembly and cancer points to this pathway as a new target for anti-cancer drugs, according to the study. Ribosomes are the targets of many commercially used antibiotics and represent a promising area of research because of the importance of ribosome assembly and function for cell growth.

“We now understand how this complicated assembly process works and we can finally show that this really is a quality control mechanism-significant advance over a discovery we made back in 2012, which we were never able to prove,” Ms. Karbstein said in the press release. “But even then, it seemed to be the most logical conclusion.”

The study was supported by the National Institutes of Health, the Howard Hughes Medical Institute, and PGA National Gold Club.

Source: The Scripps Research Institute