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 their genetic makeup. That sequence data was then matched to the messenger RNA it came from, giving the researchers a picture of exactly which RNA — and thus, which genes — were being turned into protein at a given moment in time.
Green and postdoctoral fellow Nick Guydosh, Ph.D., adapted this method to see what Dom34 was up to. Guydosh wrote a computer program to compare footprint data from yeast with and without functioning Dom34 genes. The program then determined where on messenger RNAs the ribosomes in cells without Dom34 tended to stall. It was at these points that Dom34 was rescuing the ribosomes in the normal cells, Guydosh says.
"What many of these 'traffic jams' had in common was that the RNA lacked a stop codon where the ribosome could be recycled normally," he says. For example, some of the problem messenger RNAs were incomplete — a common occurrence, as chopping up messenger RNAs is one way cells regulate how much of a protein is produced.
In others, the RNA had a stop codon, but something strange and unexpected was going on in these latter cases: The ribosomes kept going past the place where the stop codon was and went into a no man's land without protein-making instructions. "Ribosomes kept moving but stopped making protein, at least for a time," Guydosh says. "As far as we know, this 'scanning' activity has never been seen before — it was a big surprise."
"What these results show us is why we need Dom34 to survive: It's the only protein that can rescue ribosomes stuck on RNAs," says Green. "Without it, cells eventually run out of the ribosomes they need to make protein."
Link to the Cell paper: http://www.cell.com/abstract/S0092-8674%2814%2900162-7
This study was funded by the National Institute of General Medical Sciences (grant number R01GM059425), the Howard Hughes Medical Institute and the Damon Runyon Cancer Research Foundation.
Shawna Williams | EurekAlert!
Fish Oil-Diet Benefits May be Mediated by Gut Microbes
28.08.2015 | University of Gothenburg
Bio-fabrication of Artificial Blood Vessels with Laser Light
28.08.2015 | Fraunhofer-Institut für Lasertechnik ILT
A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.
The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...
A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).
Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...
In mountainous regions earthquakes often cause strong landslides, which can be exacerbated by heavy rain. However, after an initial increase, the frequency of these mass wasting events, often enormous and dangerous, declines, in fact independently of meteorological events and aftershocks.
These new findings are presented by a German-Franco-Japanese team of geoscientists in the current issue of the journal Geology, under the lead of the GFZ...
Bacteria do not cease to amaze us with their survival strategies. A research team from the University of Basel's Biozentrum has now discovered how bacteria enter a sleep mode using a so-called FIC toxin. In the current issue of “Cell Reports”, the scientists describe the mechanism of action and also explain why their discovery provides new insights into the evolution of pathogens.
For many poisons there are antidotes which neutralize their toxic effect. Toxin-antitoxin systems in bacteria work in a similar manner: As long as a cell...
It comes when called, bringing care utensils with it and recording how they are used: Fraunhofer IPA is developing an intelligent care cart that provides care staff with physical and informational support in their day-to-day work. The scientists at Fraunhofer IPA have now completed a first prototype. In doing so, they are continuing in their efforts to improve working conditions in the care sector and are developing solutions designed to address the challenges of demographic change.
Technical assistance systems can improve the difficult working conditions in residential nursing homes and hospitals by helping the staff in their work and...
20.08.2015 | Event News
20.08.2015 | Event News
19.08.2015 | Event News
31.08.2015 | Earth Sciences
28.08.2015 | Physics and Astronomy
28.08.2015 | Health and Medicine