Navigation Links
High fidelity keeps human DNA assembly line humming

Scientists at Michigan State University have made a major discovery on the inner workings of genetic coding, mapping out mechanisms of one of life's most elemental functions: RNA synthesis. Their work has crucial implications for how a normal cell forms a tumor and how a virus runs amok.

The work is published in the May 13 edition of the scientific journal Molecular Cell.

Behind the basic research is a story that melds exquisite nanotechnology in living systems and cutting-edge biochemistry and molecular biology with a system of checks and balances.

"RNA synthesis is at the hub of human genetic control. It's important for understanding cancers, viral infections and normal human development," said Zachary Burton, professor of biochemistry and molecular biology. "If you want to understand and control things like viral infections and tumors this fundamental process has to be understood in every detail. This is basic science, but basic science with practical application."

Burton and his team study how RNA is made from a DNA template. DNA is the genetic material that holds the blueprint for life. DNA dictates orders to RNA to make proteins, which give a cell its identity. Mistakes in RNA synthesis can lead to cancer or can support the life cycle of an invading virus. Researchers consider control of RNA synthesis to be a huge issue in human health. It is also the foundation of how living systems function.

In the world of molecular biology, much attention has been given to how RNA is made. Burton explains that it is similar to an industrial assembly line, with DNA being a conveyer belt to load building blocks, or bases, called nucleoside triphosphates (NTPs) to hook up with a growing strand of RNA.

Burton's insight was to discover that the NTP bases preload to the DNA template several steps before they are added to the growing RNA chain.

This idea contradicts the prevalent view of how RNA and NTP bases hook up. Preload ing of NTPs hints at a previously unknown quality control station to maintain accuracy of RNA synthesis. If an NTP doesn't match up properly with DNA, the system stalls ?and even backs up to correct the error.

"We're able to show how an error will be sensed and corrected," Burton said. "The quality control system checks NTP loading several ways. If it doesn't match the criteria, it gets booted out."

In addition to better understanding how errors are prevented, Burton's research team also learned ways errors are corrected during rapid RNA synthesis. To learn about error correction, Burton's team stalled the DNA conveyer belt. They did this using a deadly mushroom toxin, alpha-amanitin.

Alpha-amanitin is the poison of the death cap mushroom, which can be deadly to humans. In 54 A.D., Emperor Tiberius Claudius was fed a death cap mushroom by his wife Agrippina to put her son Nero on the throne of ancient Rome. Alpha-amanitin kills people by stalling movement of the DNA conveyer belt.

Finding evidence of quality control gives some perspective to the elegance of cell creation. Burton said it does not mean mistakes never occur. The assembly line analogy holds up there. The human system has an acceptable level of error required to allow for the speed at which cells must reproduce.

"RNA polymerase is one of nature's great designs," Burton said. RNA polymerases are found in bacteria, yeast, plants and humans. The design has endured because of this fidelity mechanism for RNA synthesis. "This is a tried and true design and our study explains why this is an enduring design."

The paper, "Dynamic Error Correction and Regulation of Downstream Bubble Opening by Human RNA Polymerase II," also is authored by research associates Xue Gong and Chunfen Zhang in Burton's lab and Michael Feig, MSU assistant professor of biochemistry and chemistry.


'"/>

Source:Michigan State University


Related biology news :

1. DNA from feathers tells tale of eagle fidelity
2. Nobel Laureate finds elegant explanation for DNA transcribing enzymes high fidelity
3. Gene keeps neural cells on correct developmental path
4. Life-extending protein keeps blood sugar in check
5. A resetting signal keeps circadian rhythm on track in Drosophila fruit flies
6. Unusual mechanism keeps repair protein accurate
7. Chewing up a key regulator of fat synthesis keeps mice lean despite a high-fat diet
8. Septum keeps neurons in synch, can reduce epileptic seizures by 90 percent
9. Increased sensitivity to nerve signals keeps diabetes at bay
10. A simple feedback resistor switch keeps latent HIV from awakening
11. To elude bats, a moth keeps its hearing in tune
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/26/2016)... LONDON , April 26, 2016 ... a product subsidiary of Infosys (NYSE: ... to integrate the Onegini mobile security platform with ... http://photos.prnewswire.com/prnh/20151104/283829LOGO ) The integration will ... to access and transact across channels. Using this ...
(Date:4/19/2016)... , UAE, April 20, 2016 ... be implemented as a compact web-based "all-in-one" system solution ... the biometric fingerprint reader or the door interface with ... of modern access control systems. The minimal dimensions of ... ID readers into the building installations offer considerable freedom ...
(Date:4/15/2016)... -- Research and Markets has announced the ...  report to their offering.  ,      ... gait biometrics market is expected to grow at ... Gait analysis generates multiple variables such ... compute factors that are not or cannot be ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... June 27, 2016 , ... Rolf K. Hoffmann, ... faculty of the University of North Carolina Kenan-Flagler Business School effective ... at UNC Kenan-Flagler, with a focus on the school’s international efforts, leading classes ...
(Date:6/27/2016)... 27, 2016   Ginkgo Bioworks , a leading ... was today awarded as one of the World ... world,s most innovative companies. Ginkgo Bioworks is engineering ... real world in the nutrition, health and consumer ... with customers including Fortune 500 companies to design ...
(Date:6/24/2016)... , June 24, 2016 Epic ... sensitively detects cancers susceptible to PARP inhibitors by ... tumor cells (CTCs). The new test has already ... therapeutics in multiple cancer types. Over ... DNA damage response pathways, including PARP, ATM, ATR, ...
(Date:6/24/2016)... ... , ... Researchers at the Universita Politecnica delle Marche in Ancona combed medical ... mesothelioma. Their findings are the subject of a new article on the Surviving Mesothelioma ... in the blood, lung fluid or tissue of mesothelioma patients that can help point ...
Breaking Biology Technology: