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Possible explanation for human diseases caused by defective ribosomes
Date:3/31/2014

ly hard, causing anemia and bone marrow failure early in life. Although these disorders can be medically managed with frequent blood transfusions, the bone marrow cells are subjected to an evolutionary phenomenon called "selective pressure," a process that favors reproduction of individuals that resolve problems that limit their ability to thrive. In this case, cells would be favored that could circumvent the mutation that limits the number of available ribosomes and cellular reproduction.

After a few weeks, a group of fast-growing cells appeared on the petri dish containing the mutant yeast cells. The team sequenced the genomes of these cells and found a mutation in a second gene that codes for one of the quality control inspectors. The mutation made the quality control inspector do its job less accurately. This increased the total number of ribosomes available to the cells, enabling cells with the mutation to make more protein, grow quickly, and take over the population. However, the available ribosomes were still defective: their underlying structural problems and biochemical defects never got repaired.

The researchers found that the defective ribosomes tend to make a specific kind of mistake when translating the genetic code. This mistake changes specific patterns of gene expression in cells, consistent with changes that can lead to cancer. The mistakes make an already unstable set of molecules even more unstable. One such set of molecules is important for helping cells maintain telomeresthe DNA at the ends of the chromosomes. The mutant cells exhibited shortened telomeres, a fundamental defect that has been linked to both cancer and aging. The research team proposed two different, but not mutually exclusive, explanations for the changes in gene expression: the mutant ribosomes could be directly changing patterns of gene expression and/or the second suppressor mutation could be driving the changes.

Currently, the researchers are looki
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Contact: Heather Dewar
hdewar@umd.edu
301-405-9267
University of Maryland
Source:Eurekalert  

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