The research, described this week in the journal Science and led by Illinois physics professor and Howard Hughes Medical Institute investigator Taekjip Ha, settles a debate over how the protein, RIG-I (pronounced rig-EYE), is able to distinguish between viral RNA and self (or cellular) RNA.
"RIG-I is the first molecule in the immune response to detect viral RNA," said Sua Myong, lead author on the study and a professor at the U. of I.'s Institute for Genomic Biology. Unlike most other proteins known to detect viral infections only in specialized immune cells, RIG-I is active in every cell type in the body, she said.
The RIG-I protein has two major parts: caspase-recruitment domains (CARDs) and an ATPase domain that consumes ATP, the cellular fuel molecule.
Previous studies had shown that the CARD domains actually inhibit the activity of RIG-I when no virus is present, but are vital to sounding the alarm and triggering an immune response once a certain type of virus has been detected.
Other studies had found that RIG-I recognizes an important feature of viral RNAs that is missing from most human RNAs. This feature, a "triphosphate" tag at a particular end, the "five-prime" (5') end, of viral RNA, is a viral fingerprint that tells RIG-I that something is amiss. Detection of this tag starts a cascade of reactions that allows RIG-I to broadcast a message to other cellular components, and ultimately to other cells.
The researchers also knew that RIG-I was usually active in the presence of double-stranded RNA, not the single-stranded RNA found in most animal cells.
Earlier research had also shown that the central ATPase domain is critical to the function of the molecule. A single mutation in this region shuts down its activity altogether.
"We knew that the CARD domain was responsible for transmitting the antiviral signaling," Myong said. "And we knew how the 5'-triphosphate tag is detected. But a big question remained about the ATPase domain: It was using ATP to do something – but what?"
To solve that mystery, the researchers used a technique termed "protein-induced fluorescent enhancement." This method makes use of a fluorescent dye that, when attached to a specific region of a molecule such as RNA, glows with more or less intensity depending on its proximity to a protein that is interacting with that molecule.
Using this technique, the researchers found that the RIG-I protein moves back and forth (translocates) selectively on double-stranded RNA, and that this activity is greatly stimulated in the presence of 5'-triphosphate.
By requiring both the 5'-triphosphate and the double-stranded RNA for it to function, the RIG-I protein is able to very accurately detect a viral invader, said Ha.
Most cellular RNAs have their triphosphate tails bobbed, capped or otherwise modified before circulating in the cytosol of the cell, he said. "So this is one powerful way of distinguishing viral RNA from cellular RNA."
Prior to this study, researchers did not know if RIG-I sensed both the double-stranded RNA and the 5'-triphosphate separately, or in an integrated manner, said Myong.
"Our work bridges the gap," she said. "We show that it does both in an integrated manner."
Diana Yates | EurekAlert!
Diagnoses: When Are Several Opinions Better Than One?
19.07.2016 | Max-Planck-Institut für Bildungsforschung
High in calories and low in nutrients when adolescents share pictures of food online
07.04.2016 | University of Gothenburg
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
25.10.2016 | Earth Sciences
25.10.2016 | Life Sciences
25.10.2016 | Earth Sciences