One of the most extraordinary properties of living cells is their ability to precisely reproduce themselves through processes that transfer genetic information from one cell to the next.
However, there are times when one of the steps of information transfer, transcription, goes awry at the cellular level, potentially producing diseases such as cancer and other health disorders. Unraveling how those processes work and how substandard transcription can be prevented is a major goal of biomedical science. Progress in this area may also lead the way toward development of drugs that target the genetic transcription process in disease-causing microbes.
A research team led by Arkady Mustaev, PhD, of the Public Health Research Institute (PHRI) at the University of Medicine and Dentistry of New Jersey-New Jersey Medical School, has published a study posted online by the Journal of Biological Chemistry, that describes an effort by the investigators to understand the underlying mechanisms of high precision (fidelity) of RNA synthesis by RNA polymerase, the major enzyme that promotes the transcription process. They attempted to influence the role of active center tuning (ACT) -- a mechanism they first identified -- in the process of transcription fidelity, which is the accurate copying of genetic information.
ACT is a rearrangement of the RNA polymerase catalytic center from an inactive to a catalytically proficient state. The investigators found that both reactions of NTP polymerization and hydrolytic RNA proofreading are performed by the same active center that includes two magnesium (Mg) ions coordinated by aspartate triad. The active center is normally “turned off” since it is missing one of Mg ions. Correct NTP substrates as well as misincorporated RNA residues can promote ACT by inclusion of the missing Mg ion through establishing recognition contacts in the active center. Incorrect substrates cannot trigger ACT and are rejected. The investigators also demonstrate that transcript cleavage factors Gre build on ACT mechanism by providing the residues for stabilization of catalytic Mg ion and for activation of the attacking water causing 3000-4000-fold reaction enhancement thereby strongly reinforcing proofreading.
The suggested ACT mechanism is fundamentally different from that proposed for DNA replication enzyme, DNA polymerase (DNAP) in which the active centers for DNA synthesis and proofreading are separated and discrimination between deoxy- and ribo-substrate is achieved through strict fitting requirements for the sugar rather than through active center rearrangement. In DNAP active center carboxylates stem from rigid scaffolds, while in multisubunit RNAP they reside in an apparently flexible loop. ACT is accompanied by significant re-shaping of the loop, which would not be possible in DNAP.
This study was supported by NIH grant RO1 GM-30717-21.
Journalists who wish to speak with Dr. Arkady Mustaev should contact Rob Forman, UMDNJ Chief of News Services, at 973-972-7276 or firstname.lastname@example.org .About PHRI:
Rob Forman | Newswise
The structure of the BinAB toxin revealed: one small step for Man, a major problem for mosquitoes!
30.09.2016 | CNRS (Délégation Paris Michel-Ange)
The first genome of a coral reef fish
29.09.2016 | King Abdullah University of Science and Technology
Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.
Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...
Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.
Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...
The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.
“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...
With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.
Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...
For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.
Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...
30.09.2016 | Event News
29.09.2016 | Event News
28.09.2016 | Event News
30.09.2016 | Earth Sciences
30.09.2016 | Event News
30.09.2016 | Physics and Astronomy