Glitch in protein synthesis could affect tumour growth: IISc study

The Indian Institute of Science.
| Photo Credit: The Hindu

Indian Institute of Science (IISc) researchers have found that a glitch in protein synthesis could affect tumour growth.

In a new study published in the Journal of Cell Science, Associate Professor at the Department of Biochemistry, Sandeep Eswarappa’s team zeroed in on a gene that codes for a protein called FEM1B.

They show how FEM1B mRNA readthrough plays a key role in the cell cycle, with implications for cancer cell proliferation and tumour growth.

Marking right proteins

“The FEM1B protein is part of a complex that marks other proteins for degradation. Its job is to make sure that the right proteins are marked. The complex targets key proteins involved in many cellular processes – one of them being the cell cycle, to keep a check on how much cells proliferate,” per IISc.

“In the study, the researchers found that stop codon readthrough causes the translation machinery to make a longer and more unstable version of FEM1B. Ironically, this marks FEM1B itself for degradation, leading to reduced levels of the protein. The team found that a specific nucleotide sequence at the tail end of the FEM1B gene directs this readthrough.”

According to IISc the team then became curious about how this would affect cancer cell growth – a hallmark of the deadly disease is the uncontrolled proliferation of cells. In lab-grown cancer cell lines, they deployed the CRISPR-Cas9 system – commonly used “molecular scissors” – to snip off the sequence driving the readthrough from the FEM1B gene. Preventing readthrough led to increased levels of the FEM1B protein – and therefore increased degradation of target proteins – and a delayed cell cycle. This caused the cancer cells to proliferate less.

The team then injected the readthrough-defective cancer cell lines in a mice model and found that the consequent tumours grew more slowly.

Delving into publicly available datasets of human cancer patients, the researchers also discovered that a higher expression of the FEM1B gene correlated with an increased probability of survival, which was consistent with their hypothesis.

Evolution of gene

When they looked at the evolution of the FEM1B gene, they realised that the readthrough process seems to be found specifically in humans and chimpanzees.

IISc said, “They think that this glitch might have occurred due to the insertion of a single nucleotide downstream of the first stop codon – a tiny change that happened about 10 million years ago, when humans and chimpanzees branched off from other primates. This could be one of the factors that contributed to increased susceptibility for cancer in humans compared to other primates, the authors speculate.”