Molecular Medicine Israel

Cell, Volume 147, Issue 7, 1484-1497, 23 December 2011. Abstract
Tatjana Trcek, Daniel R. Larson, Alberto Moldón, Charles C. Query and Robert H. Singer.
“Single-Molecule mRNA Decay Measurements Reveal Promoter- Regulated mRNA Stability in Yeast.”

Promoter- regulated mRNA stability in budding yeast
Promoter- regulated mRNA stability in budding yeast

Researchers uncover a self-destruct mechanism that determines the lifespan of messenger RNA molecules.

Observing single molecules in yeast cells in real time, researchers have discovered that the promoter regions of two genes involved in the cell cycle not only act to encourage transcription; they also initiate a self-destruct timer that controls when the resulting messenger RNA (mRNA) molecules are degraded. The results, published in Cell, provide some of the first clues regarding how cells manage their mRNA levels, and could have implications for controlling cell division in cancer.

“Our findings indicate that genes making proteins whose levels must be carefully controlled contain promoter regions that sentence their mRNA molecules to death even as the mRNA is being born,” senior author Robert Singer of the Gruss Lipper Biophotonics Center and Albert Einstein College of Medicine of Yeshiva University said in a press release. “Their lifespans are determined at the moment of their birth.”

Specifically, the promoter regions of SWI5 and CLB2—both genes critical for regulating the cell cycle—recruit a protein called Dbf2p to jump onto the mRNAs during transcription. In the cytoplasm, another protein, called Dbf20p, joins Dbf2p, essentially tagging the mRNA for destruction.

Due to SWI5 and CLB2’s involvement in the cell cycle, the results could be relevant for developing anti-cancer therapeutics, Singer said. “Once you gain insight into the mechanisms controlling the cell cycle and cell division, you can propose targeted therapies for regulating the uncontrolled cell division that characterizes cancer.”


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