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:5/16/2017)... , May 16, 2017   Bridge Patient ... organizations, and MD EMR Systems , an ... partner for GE, have established a partnership to ... product and the GE Centricity™ products, including Centricity ... These new integrations will allow ...
(Date:4/18/2017)... Inc., a global expert in SoC-based imaging and computing solutions, has ... features the company,s hybrid codec technology. A demonstration utilizing TeraFaces ® ... be showcased during the upcoming Medtec Japan at Tokyo Big Sight ... Las Vegas Convention Center April 24-27. ... Click here for an image of the ...
(Date:4/11/2017)... BEACH GARDENS, Fla. , April 11, 2017 ... identity management and secure authentication solutions, today announced ... contract by Intelligence Advanced Research Projects Activity (IARPA) ... for IARPA,s Thor program. "Innovation has ... onset and IARPA,s Thor program will allow us ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... October 11, 2017 , ... At ... Purple announced Dr. Suneel I. Sheikh, the co-founder, CEO and chief research scientist ... has been selected for membership in ARCS Alumni Hall of Fame . ...
(Date:10/11/2017)... ... October 11, 2017 , ... ComplianceOnline’s Medical Device Summit is back for its ... 2018 in San Francisco, CA. The Summit brings together current and former FDA office ... directors and government officials from around the world to address key issues in device ...
(Date:10/11/2017)... and LAGUNA HILLS, Calif. , Oct. 11, ... Research, London (ICR) and University of ... SkylineDx,s prognostic tool to risk-stratify patients with multiple myeloma (MM), ... nine . The University of Leeds ... funded by Myeloma UK, and ICR will perform the testing ...
(Date:10/11/2017)... ... October 11, 2017 , ... Singh Biotechnology ... drug designation to SBT-100, its novel anti-STAT3 (Signal Transducer and Activator of Transcription ... is able to cross the cell membrane and bind intracellular STAT3 and inhibit ...
Breaking Biology Technology: