Researchers at the Icahn School of Medicine at Mount Sinai say they have made a new discovery about how human cells make RNA, a molecule that functions as a set of blueprints that tell cells how to build proteins, which help bodies grow and stay healthy.
But before RNA can do its job, it has to be made correctly inside the cell. The Mount Sinai scientists found that a special helper protein called SPT5 plays a big role in this process.
In a new study published in the latest issue of Molecular Cell, a team led by Robert P. Fisher, MD, PhD, professor of oncological sciences at Mount Sinai, discovered that SPT5 makes sure RNA is copied accurately and efficiently. However, SPT5 does not work alone—it needs to be activated at just the right moment.
The researchers found that an enzyme called CDK9 acts like a traffic controller, adding phosphate tags onto different parts of the SPT5 protein. These tags, which are placed on specific regions containing phosphorylation sites, turn SPT5 on and off at key stages of the RNA-making process.
Two such regions, named CTR1 and CTR2, were thought to perform similar jobs. However, the Mount Sinai team discovered something surprising: these sites actually have opposing functions that control how fast RNA is copied from DNA. In other words, CTR1 acts like an accelerator, helping the process move quickly, while CTR2 works like a brake, slowing things down to ensure accuracy.
“Our findings challenge the previous assumption that CTR2 was redundant with CTR1,” said Fisher. “Instead, we discovered that these phosphorylation sites work together but have distinct and opposing effects on RNA polymerase II elongation speed and the output of RNA.”
The study used a chemical genetic approach in human colon cancer cells (HCT116) to systematically manipulate SPT5 phosphorylation and analyze its effects on transcriptional pausing, elongation, and termination. Key discoveries include:
These insights could have major implications for diseases like cancer, where gene expression goes awry. By better understanding how SPT5 is regulated, scientists may be able to develop new drugs that fine-tune RNA production in cells.
The post Mount Sinai Team Finds New Way Cells Control RNA appeared first on GEN - Genetic Engineering and Biotechnology News.
But before RNA can do its job, it has to be made correctly inside the cell. The Mount Sinai scientists found that a special helper protein called SPT5 plays a big role in this process.
In a new study published in the latest issue of Molecular Cell, a team led by Robert P. Fisher, MD, PhD, professor of oncological sciences at Mount Sinai, discovered that SPT5 makes sure RNA is copied accurately and efficiently. However, SPT5 does not work alone—it needs to be activated at just the right moment.
The researchers found that an enzyme called CDK9 acts like a traffic controller, adding phosphate tags onto different parts of the SPT5 protein. These tags, which are placed on specific regions containing phosphorylation sites, turn SPT5 on and off at key stages of the RNA-making process.
Two such regions, named CTR1 and CTR2, were thought to perform similar jobs. However, the Mount Sinai team discovered something surprising: these sites actually have opposing functions that control how fast RNA is copied from DNA. In other words, CTR1 acts like an accelerator, helping the process move quickly, while CTR2 works like a brake, slowing things down to ensure accuracy.
Something surprising
“Our findings challenge the previous assumption that CTR2 was redundant with CTR1,” said Fisher. “Instead, we discovered that these phosphorylation sites work together but have distinct and opposing effects on RNA polymerase II elongation speed and the output of RNA.”
The study used a chemical genetic approach in human colon cancer cells (HCT116) to systematically manipulate SPT5 phosphorylation and analyze its effects on transcriptional pausing, elongation, and termination. Key discoveries include:
- Phosphorylation of CTR1 and CTR2 acts as an “accelerator and brake” system to regulate elongation speed.
- Blocking CTR1 phosphorylation caused the RNA-copying machinery to slow down, resulting in reduced “nascent transcription,” meaning fewer new RNA molecules were being made.
- Mutation of both CTR1 and CTR2 had additive effects on splicing, termination, and cell proliferation, underscoring the critical role of coordinated SPT5 phosphorylation in maintaining gene expression and cell viability.
These insights could have major implications for diseases like cancer, where gene expression goes awry. By better understanding how SPT5 is regulated, scientists may be able to develop new drugs that fine-tune RNA production in cells.
The post Mount Sinai Team Finds New Way Cells Control RNA appeared first on GEN - Genetic Engineering and Biotechnology News.