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Sunday, January 22, 2012

MRNA kill switch

One of the ways in which cells regulate their metabolic functions is to control how much of each protein is made. Robert Singer and his colleagues from the Albert Einstein College of Medicine and the National Cancer Institute have found that some mRNAs have an internal ‘stability switch’ which causes them to decay when no longer needed.

First, a molecular biology primer. Very briefly, DNA contains genes that code for proteins.  Those genes are transcribed into mRNA, which is then translated into protein.  The amount of each protein that can be made depends largely on the number of mRNA strands that are available.  To immediately stop protein production, a cell would have to eliminate any existing mRNA strands. 

The researchers used the proteins Clb2 and Swi5 because they are tied to the cell cycle. In fact, the mRNA transcripts of these proteins decay 30 times faster during mitosis (cell division) than at other times. To figure out what was causing the CLB2 and SWI5 mRNAs to self-destruct so rapidly, the researchers tried swapping bits of those genes with bits from other genes whose mRNAs don’t decay during mitosis.  Surprisingly, swapping the internal regions of the genes (the part that tells which amino acids will be in the protein) had no effect, but replacing the promoter (the start code for RNA transcription) completely changed the mRNA turnover rate. 

The researchers suggest that as CLB2 and SWI5 are being transcribed, a specific factor is loaded onto the mRNA strand that, under the right environmental signals, initiates decay of that transcript.  In other words, each mRNA strand carries its own kill switch along with it.  Although this work was done on yeast cells (using a fluorescent microscopy technique that allowed the scientists to label and observe individual mRNA molecules), it could have implications for human cell division diseases like cancer.