Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

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

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 4,000+ scientific posters on ePosters
  • More Than 5,300+ 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

Drug Design Strategy to Improve Breast Cancer Treatment
Scientists develop novel structure-based drug design strategy aimed at altering the basic landscape of hormone-driven breast cancer treatment.
Wednesday, November 23, 2016
How Protein Senses Touch
New study reveals Piezo 1, a protein discovered in 2010, is directly responsible for sensing touch.
Tuesday, November 15, 2016
Immune Cells May Facilitate Tumor Growth
Research shows macrophages create vessel-like structures to deliver oxygen and nutrients to tumours, offering a new target for treatment.
Monday, November 14, 2016
Scientists Uncover Why Hepatitis C Vaccine is Difficult to Make
Scientists have uncovered one reason why a successful hepatitis C vaccine continues to be elusive.
Thursday, October 27, 2016
Grant to TSRI-Led Consortium Increased by $87M
NIH funding, as part of the Precision Medicine Initiative, has been increased from $120M to £207M.
Thursday, October 06, 2016
Disordered Protein 'Shape Shifts' to Avoid Crowding
Study suggests disordered protein escapes from the cell membrane when it runs out of space.
Wednesday, September 21, 2016
Antibodies that Target Holes in HIV's Defence Identified
Scientists suggest 'holes' in HIV sugar sheild can be targeted by antibodies.
Friday, September 16, 2016
'Missing Evolutionary Link' of a Widely Used Natural Drug Source Found
A well-known family of natural compounds, called “terpenoids,” have a curious evolutionary origin. In particular, one question relevant to future drug discovery has puzzled scientists: exactly how does Nature make these molecules?
Tuesday, August 30, 2016
‘Lead Actors’ in Immune Cell Development Uncovered
A new study, led by scientists at The Scripps Research Institute (TSRI), reveals a surprising twist in immune biology.
Tuesday, August 30, 2016
'Missing Evolutionary Link' of Natural Drug Source Found
Scripps Florida study finds 'missing evolutionary link' of a widely used natural drug source
Monday, August 22, 2016
4 Billion-Year-Old RNA Synthesized
TSRI are one step closer to the lab recreation of the "RNA world" of 4 billion years ago.
Wednesday, August 17, 2016
Surprising Twist in Immune Biology
TSRI researchers have found the ‘lead actors’ in immune cell development, shedding light on casues of autoimmune disease.
Wednesday, August 03, 2016
Influencing the Immune System
A TSRI study has opened the door to influencing the immune system, yielding possible boosts to vaccine efficiency and immunology.
Tuesday, August 02, 2016
Drug Candidates Reduce Abnormal Protein Production
New drug candidates improve cell ability to catch miss-folded proteins that could cause deadly diseases.
Friday, July 22, 2016
Scientists Link Bipolar Disorder to Unexpected Brain Region
Researchers from The Scripps Research Institute have found that gene within the brain’s striatum could be linked to biopolar disorder.
Wednesday, July 20, 2016
Scientific News
Big Genetics in BC: The American Society for Human Genetics 2016 Meeting
Themes at this year's meeting ranged from the verification, validation, and sharing of data, to the translation of laboratory findings into actionable clinical results.
Stem Cells in Drug Discovery
Potential Source of Unlimited Human Test Cells, but Roadblocks Remain.
Automated Low Volume Dispensing Trends
Gain a better understanding of the current and future market requirements for fully automated LVD systems.
Cancer Genetics: Key to Diagnosis, Therapy
When applied judiciously, cancer genetics directs caregivers to the right drug at the right time, while sparing patients of unnecessary or harmful treatments.
Diabetes Missing Link Discovered
Researchers from the University of Auckland have shown that beta catenin plays a vital role in the control of insulin release from the pancreas.
Study Reveals New Role for Hippo Pathway in Suppressing Cancer Immunity
Hippo pathway signaling regulates organ size by moderating cell growth, apoptosis and stem cell renewal, but dysregulation contributes to cancer development.
Biological Link between the Gut Microbiome and Parkinson’s Disease
The findings suggest that targeting the gut microbiome may provide a new approach for diagnosing and treating Parkinson’s disease.
How the Brain Recognizes Faces
Machine-learning system spontaneously reproduces aspects of human neurology.
Boosting Effectiveness of Asthma Therapy
A team of scientists from UCSF has developed a new treatment to dampen bronchospasm.
Improved Stability, Shelf Life of Protein Drugs
Study improves protein drug stability and extend their shelf life by tested a novel route for non-covalent protein modification.
Scroll Up
Scroll Down
Skyscraper Banner

SELECTBIO Market Reports
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
4,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,300+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!