Surprising Mechanism Aids Cell Self Destruction

RNA strands prompt cell suicide

(RxWiki News) Excess amounts of fat and sugar force cells to self destruct when they can no longer stand the toxic environment. Scientists believe they now know why these overloaded cells commit suicide.

Researchers at Washington University School of Medicine in St. Louis have found that molecules leading to cell self destruction are not proteins as they expected. Instead they are small strands of RNA, a chemical relative to DNA.

"Understanding cell death could lead to new treatments."

The small RNAs play a role in building proteins so investigators were surprised they contributed to killing cells. The research, published in Cell Metabolism, is the first to link RNA molecules to the cellular damage characteristic of common metabolic diseases like diabetes.

Dr. Jean E. Schaffer, a cardiologist and the Virginia Minnich Distinguished Professor of Medicine at Washington University said that when the three RNAs are present, the cells die in response to metabolic stress, such as exposure to large amounts of fats and sugars. However, the cells do not die if the three RNAs are missing.

Cell suicide protects healthy tissues from damaged cells. But if a cell death pathway is shuttered, damaged cells can divide and lead to cancer. Excess cell death from abnormal metabolites such as high fats and sugars impairs the function of tissues in the body and is linked to diabetes complications and heart failure.

Schaffer and her colleagues used a genetics experiment to identify a genetic region that, when disabled, allows cells to continue living in high-fat, high-sugar conditions. While the region codes for a protein, they demonstrated that the protein itself is not involved in initiating cell death.

The team reintroduced the protein, but the cell was still unable to commit suicide. Researchers then examined non-protein-coding areas of the same region. They selectively deleted small RNAs embedded in the region’s non-coding portion, and realized that a mutation in this region protects the cells because it eliminates the small RNAs, not because it eliminates the protein.

In addition to promoting cell death from nutrient excess, the three small nucleolar RNAs promote more general mechanisms of cell death in diseased tissues.

Review Date: 
July 7, 2011