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

Ribosomes are essential for life, generating all of the proteins required for cells to grow. Mutations in some of the proteins that make ribosomes cause disorders characterized by bone marrow failure and anemia early in life, followed by elevated cancer risk in middle age. These disorders are generally called "ribosomopathies."

How can ribosomopathies first appear as diseases caused by too few cells, but later turn into diseases caused by too many cells? This paradox has puzzled the scientific community for years. A new study, which uses a genetic approach to examine this paradox, suggests ribosomopathies are caused by a sequence of mistakes at the molecular level.

The study proposes a detailed version of this basic chain of events: Some people are born with or acquire a gene mutation that causes defective ribosomes to be produced. A quality control system in cells eliminates most of the faulty ribosomes. This leaves few ribosomes available for cells to use to produce required proteins, which causes anemia and bone marrow failure early in life. Next, a second gene mutation suppresses the quality control system, making more ribosomes available to cells. However, the available ribosomes are defective and cause changes in gene expression patterns that can result in cancer.

The study will be published the week of March 31, 2014 in the online early edition of the journal Proceedings of the National Academy of Sciences. The research was partly supported by the National Institutes of Health.

"Making ribosomes is a lot like making carsthere is an intricate cellular assembly line where many different parts are brought together to make a complex, fine-tuned, high-performance machine. The assembly line contains quality control inspectors located at critical points in the process to ensure that machines with defective parts do not make it out of the factory and onto the roads," said Jonathan Dinman, professor in the Department of
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Contact: Heather Dewar
hdewar@umd.edu
301-405-9267
University of Maryland
Source:Eurekalert  

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