The idea that RNA (ribonucleic acid) is involved in activating and inhibiting genes is relatively new, and it has been unclear how RNA strands might regulate the process.
Genes are segments of DNA housed in the nucleus of every cell, and they carry instructions for making proteins. Faulty or mutated genes lead to malfunctioning, missing or overabundant proteins, and any of those conditions can result in disease. Scientists seek to understand the mechanisms by which genes are activated, or expressed, and turned off in order to get a clearer picture of basic cell biology and also to develop medical therapies that affect gene expression.
In previous studies, Dr. Corey and Dr. Bethany Janowski, assistant professor of pharmacology at UT Southwestern and a senior author of the current study, have shown that tiny strands of RNA can be used to activate certain genes in cultured cancer cells. Using strands of RNA that they manufactured in the lab, the researchers showed that the strands regulate gene expression by somehow perturbing a delicate mixture of proteins that surround DNA and control whether or not genes are activated.
Until now, however, it was not clear exactly how the synthetic RNA strands affected that mix of regulating proteins.
In the current study, also carried out in cancer cell cultures, the UT Southwestern research team discovered an unexpected target for the manufactured RNA. The RNA did not home in on the gene itself, but rather on another type of RNA produced by the cell, a so-called noncoding RNA transcript. This type of RNA is found in association with the promoter regions that occur in front of the gene. Promoter regions, when activated, act essentially as a “start” command for turning on genes.
The researchers found that their man-made RNA strand bound to the RNA transcript, which then recruited certain proteins to form an RNA-protein complex. The whole complex then bound to the promoter region, an action that could then either activate or inhibit gene expression.
“Involvement of RNA at a gene promoter is a new concept, potentially a big new concept,” Dr. Janowski said. “Interactions at gene promoters are critical for understanding disease, and our results bring a new dimension to understanding how genes can be regulated.”
Until recently, many scientists believed that proteins alone control gene expression at promoters, but Drs. Corey and Janowski’s results suggest that this assumption is not necessarily true.
“By demonstrating how small RNAs can be used to recruit proteins to gene promoters, we have provided further evidence that this phenomenon should be in the mainstream of science,” Dr. Corey said.
Although using synthetic RNA to regulate gene expression and possibly treat disease in humans is still in the future, Dr. Corey noted that the type of man-made RNA molecules employed by the UT Southwestern team are already being used in human clinical trials, so progress toward the development of gene-regulating drugs could move quickly.
Other researchers from UT Southwestern involved in the research were lead author and student research assistant Jacob Schwartz; student research assistant Scott Younger; and research associate Ngoc-Bich Nguyen. Researchers from the University of Western Ontario and ISIS Pharmaceuticals also participated.
The research was supported by the National Institutes of Health and the Welch Foundation.
Amanda Siegfried | EurekAlert!
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences