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.”
Ha is also an affiliate of the Institute for Genomic Biology and co-director of the Center for the Physics of Living Cells at Illinois.
Funding for this research was provided by the National Institute of General Medical Sciences and the National Science Foundation.
Editor’s note: To reach Sua Myong, call 217-244-5057; email: firstname.lastname@example.org
To reach Taekjip Ha, call 217-265-0717; email: email@example.com
Further reports about: > 5’-triphosphate > ATP > ATPase > Card > Genomic Biology > Illinois River Watershed > RIG-I > RNA > Science TV > caspase-recruitment domains > cellular RNAs > cellular protein > genomic > immune cell > immune response > protein-induced fluorescent enhancement > synthetic biology > viral infection > viruses
The birth of a new protein
20.10.2017 | University of Arizona
Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research