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.”
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 | newswise
Making fuel out of thick air
08.12.2017 | DOE/Argonne National Laboratory
‘Spying’ on the hidden geometry of complex networks through machine intelligence
08.12.2017 | Technische Universität Dresden
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications
Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...
Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.
The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...
Transistors based on carbon nanostructures: what sounds like a futuristic dream could be reality in just a few years' time. An international research team working with Empa has now succeeded in producing nanotransistors from graphene ribbons that are only a few atoms wide, as reported in the current issue of the trade journal "Nature Communications."
Graphene ribbons that are only a few atoms wide, so-called graphene nanoribbons, have special electrical properties that make them promising candidates for the...
08.12.2017 | Event News
07.12.2017 | Event News
05.12.2017 | Event News
08.12.2017 | Life Sciences
08.12.2017 | Information Technology
08.12.2017 | Information Technology