Corporate Banner
Satellite Banner
Genotyping & Gene Expression
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

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

Join For Free

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 2,900+ scientific posters on ePosters
  • More than 4,200+ 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 TechnologyNetworks.com 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.

Related Content

Silencing X Chromosomes
Work could lead to ways to counteract X-linked diseases in girls and women.
Tuesday, January 12, 2016
Precision Medicine for Penile Cancer
Defining the genomic landscape reveals similarities with other squamous cell cancers.
Thursday, December 17, 2015
Adrenals Run Amok
Each of your kidneys wears a little yellow cap that helps keep your blood pressure in check, and much more. But in some people, it starts running amok, pumping out a hormone that sends blood pressure sky-high.
Friday, August 14, 2015
A Roadblock to Personalized Cancer Care
Experts call for more support for tumor biomarker tests; fixing a vicious cycle will lead to tests that better predict treatment success.
Tuesday, August 06, 2013
Study Finds Potential to Match Tumors with Known Cancer Drugs
Mapping the landscape of kinases could aid in new world of personalized cancer treatment.
Friday, February 08, 2013
University of Michigan Study Shows SEQUENOM's MassARRAY Technology Identifies HPV Infections
New study uncovers significant proportion of potential false negatives in widely used HPV DNA test which could lead to cervical cancer.
Tuesday, July 21, 2009
Confusing Risk Information may Lead to Poor Cancer Treatment Choices
Tools designed to help guide treatment decisions are too complex for most patients to understand, U-M study finds.
Wednesday, December 10, 2008
U-M Study: Herceptin Targets Breast Cancer Stem Cells
The gene, HER2, causes cancer stem cells to multiply and spread, explaining why HER2 has been linked to a more aggressive type of breast cancer.
Thursday, July 10, 2008
Cancer Drug Works by Overactivating Cancer Gene
Michigan researchers have discovered that a promising cancer drug is able to strike a blow against melanoma tumor cells by revving up the action of a cancer-promoting gene.
Friday, November 23, 2007
Researchers Use New Method to Discover Gene Rearrangements
Genes rearrangements in prostate cancer cells may play a role in the development and progression of the disease.
Tuesday, November 01, 2005
Scientific News
Common Cell Transformed into Master Heart Cell
By genetically reprogramming the most common type of cell in mammalian connective tissue, researchers at the University of Wisconsin—Madison have generated master heart cells — primitive progenitors that form the developing heart.
Genetic Mutation that Prevents Diabetes Complications
The most significant complications of diabetes include diabetic retinal disease, or retinopathy, and diabetic kidney disease, or nephropathy. Both involve damaged capillaries.
Charting Kidney Cancer Metabolism
Changes in cell metabolism are increasingly recognized as an important way tumors develop and progress, yet these changes are hard to measure and interpret. A new tool designed by MSK scientists allows users to identify metabolic changes in kidney cancer tumors that may one day be targets for therapy.
Individuals' Medical Histories Predicted by their Noncoding Genomes
Researchers have found that analyzing mutations in regions of the genome that control genes can predict medical conditions such as hypertension, narcolepsy and heart problems.
'Molecular Movie' Opens Door to New Cancer Treatments
An international team of scientists led by the University of Liverpool has produced a 'structural movie' revealing the step-by-step creation of an important naturally occurring chemical in the body that plays a role in some cancers.
Custom Tuning Knobs to Turn Off Any Gene
Factory managers can improve productivity by telling workers to speed up, slow down or stop doing tangential tasks while assembling widgets. Unfortunately for synthetic biologists attempting to produce pharmaceuticals, microbes don’t respond to direction like human personnel.
Unique Mechanism for a High-Risk Leukemia
Researchers uncovered the aberrant mechanism underlying a notoriously treatment-resistant acute lymphoblastic leukemia subtype; findings offer lessons for understanding all cancers.
Genetically Mapping the Most Lethal E.Coli Strains
New approach could lead to fewer deaths, and new treatments.
The Spice of Life
Scientists discover important genetic source of human diversity.
Cytoskeleton Crew
Findings confirm sugar's role in helping cancers survive by changing cellular architecture.
SELECTBIO

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
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!