Discovering the Mechanisms That Fine-tune Gene Expression 

Turning on or off one or more genes at the wrong time or in the wrong cells can dramatically alter their activity and lead to unrestrained growth and cancer. Therefore, numerous control mechanisms are in place to keep the whole process in check.

Because of the complexity of gene expression regulation, this is one of the most intensely studied subjects.

In a new study published in the prestigious journal Cell, the lab of Dr. Alessandro Gardini and collaborators at the Peter MacCallum Cancer Centre in Melbourne, Australia, discovered a new mechanism that fine-tunes gene expression and is disrupted in cancer, indicating a possible new avenue for cancer treatment.

RNA transcription is the first step in the flow of genetic information from DNA to proteins. This is a very dynamic process operated by an enzyme called RNA polymerase II (RNAPII) and is tightly controlled through the opposing functions of several proteins. 

After starting transcription, RNAPII comes to a pause to allow the cell to check that the process is taking place smoothly and with no incidents. Shortly after, the enzyme starts transcribing again and elongating the newly synthesized RNA molecule.

Gardini and team uncovered a new regulatory checkpoint in which two proteins work in tandem to control the balance between pausing and elongation.

“Cancer is a consequence of altered gene expression,” said Gardini. “We described one of the essential ways through which gene transcription is kept in check.”

Researchers also showed that blocking one protein and activating the other at the same time represents a new potential strategy for combination treatment, demonstrating activity in preclinical models of leukemia and solid malignancies.

Overall, this study provided new insight into how gene expression is tightly controlled and opened new avenues for transcription-based anticancer therapy.

To learn more about this research, read our press release.