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

Discovery of Biological Energy-Sensing Switch Could Have Broad Implications for Biology and Medicine

Published: Tuesday, October 23, 2012
Last Updated: Tuesday, October 23, 2012
Bookmark and Share
Biochemists at The Scripps Research Institute (TSRI) have discovered a genetic sequence that can alter its host gene’s activity in response to cellular energy levels.

The scientists have found this particular energy-sensing switch in bacterial genes, which could make it a target for a powerful new class of antibiotics. If similar energy-sensing switches are also identified for human genes, they may be useful for treating metabolism-related disorders such as type 2 diabetes and heart disease.

“This discovery adds a new dimension to our understanding of how cells sense and manage their energy levels, which is one of the most important processes in biology,” said the study’s senior author, Martha J. Fedor, a professor the departments of Chemical Physiology and Molecular Biology and a member of the Skaggs Institute for Chemical Biology at TSRI.

The findings are described online ahead of print on October 21, 2012, in the journal Nature Chemical Biology.

A Fuel Sensor

This type of gene-switching sequence is known as a riboswitch because it appears on the strand of ribonucleic acid (RNA) that is first transcribed from a gene’s DNA. Unlike other known riboswitches, which have relatively limited functions, this one acts as a sensor for the basic molecular fuel that powers all living cells and controls many genes.

The newly discovered riboswitch detects a small molecule known as adenosine triphosphate (ATP), the standard unit of chemical energy in all known organisms on our planet. Scientists had thought that cells use only large and relatively complex proteins to sense these all-important energy molecules and adjust cell activities accordingly. No one had found ATP sensors among riboswitches, which can alter cell activity at a more fundamental level—usually by interrupting a gene’s transcription from DNA.

Moreover, previously described riboswitches are relatively simple feedback sensors that affect narrow metabolic pathways. Most of them merely sense and adjust the expression rate of their own host gene. “This is the first riboswitch that is known to be involved in global metabolic regulation,” said Fedor.

In recent years, the Fedor team had found hints that such a riboswitch could exist. Many RNA sequences with possible riboswitch activity had never been characterized, and several riboswitches in bacteria sense molecules that are closely related to ATP. Fedor and a graduate student in her laboratory, Peter Y. Watson, therefore set out to find bacterial riboswitches that could indeed sense ATP.

Caught in the Act

The task was more challenging than it might have seemed. Watson could not simply expose suspected riboswitches to ATP and see which ones stuck best to the energy molecules. ATP is present in high concentrations in cells, and its interactions with its known protein sensors are necessarily fleeting, low-affinity affairs. Interactions with a riboswitch would be expected to look the same. “Such interactions are really too weak to be detected using traditional methods,” Watson said. But he found evidence that an RNA interaction with an ATP-like molecule would occur in a way that allows the brief coupling to be caught in the act—using a burst of ultraviolet radiation, which can create a strong chemical crosslink between two molecules.

In this way, he discovered a stretch of apparent ATP-binding RNA known as the ydaO motif. Watson performed structure-mapping analyses of ydaO to confirm that it binds to ATP and to determine precisely where it binds. Attaching ydaO to a “reporter” gene, he found that in bacterial cells, the reporter gene’s expression level stayed low when ATP levels were normal and rose sharply when ATP levels dropped—as would be expected if ydaO is really an ATP-sensing riboswitch. Even in unaltered cells of a test bacterium, B. subtilis, levels of the genes that normally contain the ydaO motif rose and fell in the same way in response to changing ATP levels.

The ydaO motif occurs in the large subset of bacteria known as gram-positive bacteria. Across these bacterial species, it has been found, to date, on 580 separate genes. “These ydaO-regulated genes encode proteins that have a wide variety of functions, from cell wall metabolism to amino acid transport,” Watson said. “It makes sense that a riboswitch in control of such disparate processes would be responding to a central metabolite such as ATP.”

New Possibilities

The finding has basic scientific importance because it is the first known example of a riboswitch that binds ATP; it is also the first known riboswitch that has such broad regulatory functions. “It opens up the possibility that RNA switches are involved in the general regulation of metabolism,” said Fedor.

The fact that ydaO motifs serve as “off-switches” for key bacterial genes also makes them a potential target for new antibiotics. “Hitting these riboswitches with a small-molecule, ATP-mimicking drug so that they can’t turn on genes that promote bacterial growth and survival could be a viable approach,” said Fedor.

Her laboratory will now search for other ATP-sensing riboswitches in bacteria and in higher organisms, including humans. A human ATP-sensing riboswitch, if targeted appropriately by drugs, might be able to alter cell activity in ways that help treat common metabolic disorders. Type 2 diabetes, which presently affects several hundred million people worldwide, is known to feature the improper regulation of ATP levels in cells.

Funding for the study, “The ydaO motif is an ATP-sensing riboswitch in Bacillus subtilis,” was provided by the Skaggs Institute for Chemical Biology at TSRI.

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.

Related Content

Potential Target for Treatment of Autism
Grant of $2.4 million will support further research.
Friday, October 02, 2015
Key Morphine Regulator Identified
The findings could lead to less addictive pain medications.
Thursday, September 24, 2015
Scientists Make Strides in Therapy Preventing Addiction Relapse
Single Injection of Drug Candidate Prevents Meth Relapse in Animal Models.
Thursday, August 06, 2015
Search for Cancer Drug Candidates
Scripps Florida scientists awarded $1.2 million to find drug candidates that could treat a wide range of cancers.
Friday, April 10, 2015
Scripps Florida Scientists Win $1.5 Million Grant to Develop New Cancer Drugs
Scientists from the Florida campus of The Scripps Research Institute (TSRI) have been awarded a $1.5 million grant from the National Institutes of Health (NIH) to develop drug candidates that could treat cancer and neurodegenerative disease.
Tuesday, March 24, 2015
Possible Neuron Killing Mechanism Behind Alzheimer’s and Parkinson’s Diseases Discovered
$1.4 million grant will enable team to follow up with search for drug candidates.
Tuesday, February 17, 2015
New Targets and Test to Develop Treatments for Memory Disorders
The study focuses on kinesin, a molecular motor protein that plays a role in the transport of other proteins throughout a cell.
Thursday, November 13, 2014
Chemists Discover Cancer Drug Candidate Structure
Chemists at The Scripps Research Institute have determined the correct structure of a highly promising anticancer compound approved by the U.S. FDA for clinical trials in cancer patients.
Wednesday, May 21, 2014
Scripps Research Institute Creates New Drug Discovery Initiative
Scripps Advance is a new drug discovery initiative to translate early-stage biomedical research projects into clinical development candidates.
Wednesday, April 16, 2014
Innovative Screening Strategy Swiftly Uncovers New Drug Candidates, New Biology
Method has been utilised to identify compound with promise for obesity-linked diabetes.
Tuesday, December 24, 2013
New Findings from The Scripps Research Institute Could Help Improve Development of Drugs for Addiction
Scientists have described findings that could enable the development of more effective drugs for addiction with fewer side effects.
Thursday, August 08, 2013
Study Reveals How Serotonin Receptors Can Shape Drug Effects from LSD to Migraine Medication
A team of scientists has determined and analyzed the high-resolution atomic structures of two kinds of human serotonin receptor.
Tuesday, March 26, 2013
Scripps Research Scientists Create Novel RNA Repair Technology
Discovery could aid search for Huntington’s, Spinocerebellar Ataxia, and Kennedy Disease treatments.
Thursday, January 19, 2012
Scripps Florida Opens its Screening Technology to Florida Scientists
Program invites scientists from Florida universities and other academic research institutions to use screening technologies.
Monday, January 23, 2006
Proteomics Helps in Detecting Breast Cancer Proteins
Proteins, associated with breast cancer, can potentially be used as markers for detection or prevention or as targets for the design of drugs to treat the disease.
Monday, September 12, 2005
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
Potential Treatment for Life-Threatening Viral Infections Revealed
The findings point to new therapies for Dengue, West Nile and Ebola.
World’s First Therapeutic Venom Database
Open-source library describes nearly 43,000 effects on the human body.
Measuring microRNAs in Blood to Speed Cancer Detection
A simple, ultrasensitive microRNA sensor holds promise for the design of new diagnostic strategies and, potentially, for the prognosis and treatment of pancreatic and other cancers.
Potential Persistent Tuberculosis Treatment
Researchers have discovered several first-in-class compounds that target hidden TB infections by attacking a critical process the bacteria use to survive in the hostile environment of the lungs.
Metabolic Profiles Distinguish Early Stage Ovarian Cancer with Unprecedented Accuracy
Studying blood serum compounds of different molecular weights has led scientists to a set of biomarkers that may enable development of a highly accurate screening test for early-stage ovarian cancer.
The Do’s and Don’ts of SPR Experiments
Surface Plasmon Resonance (SPR) is a technique that is becoming more widely used, particularly by anyone who wants to obtain accurate on (association) and off (dissociation) rates for biomolecular binding.
Long-Sought Protein Sensor for the ‘Sixth Sense’ Discovered
In a study led by scientists from The Scripps Research Institute (TSRI)the sensor protein for propioception has been identified.
New Anti-Malarial Drug Screening Model
University of South Florida researchers demonstrate novel chemogenomic profiling to identify drug targets for the most lethal strain of malaria.
Shedding Light on “Dark” Cellular Receptors
UNC and UCSF labs create a new research tool to find homes for two orphan cell-surface receptors, a crucial step toward finding better therapeutics and causes of drug side effects.

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