Using a powerful data-crunching technique, Johns Hopkins researchers have sorted out how a protein keeps defective genetic material from gumming up the cellular works. The protein, Dom34, appears to "rescue" protein-making factories called ribosomes when they get stuck obeying defective genetic instructions, the researchers report in the Feb. 27 issue of Cell.
"We already knew that binding to Dom34 makes a ribosome split and say 'I'm done,' and that without it, animals can't survive," says Rachel Green, Ph.D., a professor in the Department of Molecular Biology and Genetics at the Johns Hopkins University School of Medicine and a Howard Hughes Medical Institute investigator. "In this study, we saw how the protein behaves in 'real life,' and that it swoops in only when ribosomes are in a very particular type of crisis."
Ribosomes use genetic instructions borne by long molecules called messenger RNA to make proteins that cells need to get things done. Normally, ribosomes move along strands of messenger RNA, making proteins as they go, until they encounter a genetic sequence called a stop codon. At that point, the protein is finished, and specialized recycling proteins help the ribosome disconnect from the RNA and break up into pieces.
Those pieces later come together again on a different RNA strand to begin the process again. From Green's earlier work with Dom34, it appeared that the protein might be one of the recycling proteins that kicks in at stop codons.
To see if that was the case, Green used a method for analyzing the "footprints" of ribosomes developed at the University of California, San Francisco. In 2009, scientists there reported they had mashed up yeast (a single-celled organism that is genetically very similar to higher-order animals) and dissolved any RNA that wasn't protected inside a ribosome at the time. They then took the remaining bits of RNA those that had been "underfoot" of ribosomes and analyzed the
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Johns Hopkins Medicine