Navigation Links
Protein 'rescues' stuck cellular factories

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."


Contact: Shawna Williams
Johns Hopkins Medicine

Related biology news :

1. Protein key to cell motility has implications for stopping cancer metastasis
2. Fruit flies help uncover tumor-preventing protein complex
3. Diets high in animal protein may help prevent functional decline in elderly individuals
4. Phosphorylation of tau protein in rats subjected to cerebral ischemia-reperfusion injury
5. New probes from Scripps research quantify folded and misfolded protein levels in cells
6. Characterization of stink bug saliva proteins opens door to controlling pests
7. A key protein is discovered as essential for malaria parasite transmission to mosquitos
8. A*STAR scientists discover proteins role in human memory and learning functions
9. Mitosis mystery solved as role of key protein is confirmed
10. Superbright and fast X-rays image single layer of proteins
11. New insight into protein misfolding in neurodegenerative disorders
Post Your Comments:
(Date:10/29/2015)... 29, 2015  The J. Craig Venter Institute (JCVI) ... Synthesis and Biosecurity: Lessons Learned and Options for the ... and Human Services guidance for synthetic biology providers has ... --> --> Synthetic biology ... potential to pose unique biosecurity threats. It now is ...
(Date:10/29/2015)... 2015 Today, LifeBEAM , a ... 2XU, a global leader in technical performance sports ... with advanced bio-sensing technology. The hat will allow ... key biometrics to improve overall training performance. As ... will bring together the most advanced technology, extensive ...
(Date:10/26/2015)... and LAS VEGAS , Oct. ... Labs , an innovator in modern authentication and a ... announced the launch of its latest version of the ... enabling organizations to use standards-based authentication that supports existing ... S3 Authentication Suite is ideal for organizations deploying customer-facing ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... -- Halozyme Therapeutics, Inc. (NASDAQ: HALO ) will be presenting ... on Wednesday, December 2 at 9:30 a.m. ET/6:30 a.m. ... will provide a corporate overview. th Annual Oppenheimer ... p.m. ET/10:00 a.m. PT . Jim Mazzola , vice ... overview. --> th Annual Oppenheimer Healthcare Conference in ...
(Date:11/24/2015)... ... November 24, 2015 , ... Copper is an essential micronutrient ... to proteins, copper is also toxic to cells. With a $1.3 million award ... will conduct a systematic study of copper in the bacteria Pseudomonas aeruginosa (P. ...
(Date:11/24/2015)... QUEBEC CITY , Nov. 24, 2015 /PRNewswire/ - ... the request of IIROC on behalf of the Toronto ... this news release there are no corporate developments that ... price. --> --> ... --> . --> Aeterna Zentaris ...
(Date:11/24/2015)... 2015 --> ... "Oligonucleotide Synthesis Market by Product & Services (Primer, Probe, ... DNA, RNAi), End-User (Research, Pharmaceutical & Biotech, Diagnostic Labs) ... market is expected to reach USD 1,918.6 Million by ... CAGR of 10.1% during the forecast period. ...
Breaking Biology Technology: