Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Smallest and Fastest-Known RNA Switches Provide New Drug Targets

Published: Monday, October 08, 2012
Last Updated: Monday, October 08, 2012
Bookmark and Share
Researchers say these rare, fleeting structures are prime targets for the development of new antiviral and antibiotic drugs.

Once believed to merely store and relay genetic information, RNA is now known to be a cellular Swiss Army knife of sorts, performing a wide variety of tasks and morphing into myriad shapes.

Over the past decade, researchers have determined that most of the DNA in our cells is used to make RNA molecules, that RNA plays a central role in regulating gene expression, and that these macromolecules act as switches that detect cellular signals and then change shape to send an appropriate response to other biomolecules in the cell.

While RNA's switching function has been well-documented, Hashim Al-Hashimi and his U-M colleagues report online Oct. 7 in the journal Nature a new class of switches that are significantly smaller and orders of magnitude faster than the other known class of RNA switches.

Al-Hashimi calls these short-lived structures, which were detected using a new imaging technique developed in his laboratory, micro-switches.

"We're finally able to zoom in on these rare, alternative forms of RNA that exist for just a split second and then are gone," said Al-Hashimi, the Robert L. Kuczkowski Professor of Chemistry and Biophysics.

"These things are so difficult to see because they exist for roughly 1 percent of the time and for only a microsecond to a millisecond."

In biology, a molecule's three-dimensional shape determines its properties and affects its function. RNA molecules are made of single chains that can remain stretched out as long threads or fold into complex loops with branching, ladder-like arms.

The micro-switches described by the U-M researchers involve temporary, localized changes of RNA structure into alternative forms called excited states. The structural change is the switch: the shape shift transmits biological signals to other parts of the cell.

"These excited states correspond to rare alternative forms that have biological functions," Al-Hashimi said. "These alternative forms have unique architectural and chemical features that could make them great molecules for drugs to latch onto. In some sense, they provide a whole new layer of drug targets."

In their Nature report, the U-M researchers looked at transient structural changes in three types of RNA molecules. Two of the RNAs came from the HIV virus that causes AIDS and are known to play a key role in viral replication. The third is involved in quality control inside the ribosome, the cellular machine that assembles proteins.

The newly found excited states of all three of these RNAS provide potential targets for drug development: antiviral drugs that would disrupt HIV replication and antibiotics that would interfere with protein assembly in bacterial ribosomes.

Evidence for the existence of these tiny RNA switches has been mounting for years. But until now, they're evaded detection because they are simply too small and too short-lived to be captured by conventional imaging techniques, Al-Hashimi said.

To make their discovery, the team used a modified form of nuclear magnetic resonance spectroscopy, along with a strategy for trapping and capturing the transient RNA structures. In a finding reported last year in Nature, the researchers used similar NMR techniques to catch the rare instances when bases in the DNA double helix roll back and forth.

In recent years, Al-Hashimi and his co-workers have also used NMR to create "nanovideos" that revealed in three dimensions how RNA molecules change shape—twisting, bending and rotating about their structural joints.

In addition to Al-Hashimi, authors of the Nature report are U-M's Elizabeth Dethoff, Katja Petzold, Jeetender Chugh and Anette Casiano-Negroni. Al-Hashimi is an adviser to, and holds an ownership interest in, Nymirum Inc., an RNA-based drug discovery company in Ann Arbor.

The research was supported by the National Institutes of Health and by a Rackham Graduate Student Research Grant awarded by the University of Michigan. The authors of the Nature paper acknowledge the Michigan Economic Development Cooperation and the Michigan Technology Tri-Corridor for the support of the purchase of a 600 MHz spectrometer used in the study.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Scientific News
New Analysis Technique for Chiral Activity in Molecules
Professor Hyunwoo Kim of the Chemistry Department and his research team have developed a technique that can easily analyze the optical activity of charged compounds by using nuclear magnetic resonance (NMR) spectroscopy.
Miniaturizable Magnetic Resonance
Microscopic gem the key to new development in magnetic lab-on-a-chip technology.
“Golden Window” in Deep Brain Imaging Opened
The neuroscience community is saluting the creation of a “Golden Window” for deep brain imaging by researchers at The City College of New York led by biomedical engineer Lingyan Shi.
How Viruses Commandeer Human Proteins
Researchers have produced the first image of an important human protein as it binds with ribonucleic acid (RNA), a discovery that could offer clues to how some viruses, including HIV, control expression of their genetic material.
Human Dark Proteome Initiative Launched
Group to focus on advancing research on intrinsically disordered proteins to better understand catastrophic diseases.
Clearest Ever Images of Enzyme that Plays Key Roles in Aging, Cancer
UCLA-led research on telomerase could lead to new strategies for treating disease
Analyzing Protein Structures in Their Native Environment
Enhanced-sensitivity NMR could reveal new clues to how proteins fold.
Proteins with ALS, Cancer Role Do Not Assume a Regular Shape
Our cells contain proteins, essential to functions like protein creation and DNA repair but also involved in forms of ALS and cancer, that never take a characteristic shape, a new study shows.
Studying Bowel Disease With Raman Spectroscopy
inVia confocal Raman microscope used in the study of various childhood diseases.
Pittcon Announces Sanford Asher as Recipient of the 2016 SACP Award
Asher will accept this prestigious award at Pittcon 2016 in Atlanta, Georgia.

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos