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

Stanford Biologists Watch RNA Fold in Real Time

Published: Monday, October 22, 2012
Last Updated: Monday, October 22, 2012
Bookmark and Share
Using optical tweezers and sub-nanoscale precision, Steven Block and Kirsten Frieda follow the process – and the consequences – of RNA folding.

In a soundproofed, vibration-stabilized, temperature-controlled room, Stanford biophysicist Steven Block was watching a very small origami project.

"The apparatus is so sensitive that, if you talk in the room, the vibrations in the air disturb the movement you're trying to measure," he said quietly. On a black-and-white monitor, two microscopic plastic beads were being slowly drawn apart.

Although we couldn't see it even at this high level of magnification, between the beads was stretched a single strand of RNA, folding up in real time.

Because RNA nucleotides are so small – each is only nanometers long – these effects had never been directly observed before. The Block Lab apparatus is so precise, it can measure distances to within the diameter of a hydrogen atom.

But Block's feat isn't remarkable only for its sensitivity. How RNA molecules fold is a longstanding biological problem. It's crucial for the molecules' function, and different RNA configurations play a fundamental regulatory role during the transcription of those very RNA molecules.

"Issues of gene control are arguably more important than the genes themselves," Block said. "What differentiates organisms are not the genes per se, it's which genes get expressed where and when."
Block, a professor of applied physics and of biology, and graduate student Kirsten Frieda published their findings today in the journal Science.

Laser traps

The key to the "tour-de-force of instrumentation," as Block punned, was the use of "optical tweezers." When placed in the path of a highly focused laser, the team's tiny beads were attracted to the center of the beam, where the electric field produced by the light is strongest. The researchers were thereby able to position and immobilize the beads with extreme consistency and accuracy.

In Block's elegant setup, a single molecule of RNA polymerase – the enzyme that transcribes DNA strands into RNA – was attached to one bead, while the emerging RNA transcript was linked to the other.

By keeping the tension between the two beads constant and measuring the distance between them as they moved apart, Block was able to gauge the changing length of the new RNA strand.

"What we got was a blow-by-blow readout of how RNA folds as it is processed by RNA polymerase," said Block.

Switching the riboswitch

In the case of the RNA transcript studied by Block and Frieda, there were two conformation options, which led to two very different functional results.

The "favored" option – about 10 billion times more likely to form, all things being equal – was a terminator structure that would stop transcription if it formed.

The other structure was an anti-terminator formed by an RNA element known as a riboswitch located a little upstream of the terminator. Riboswitches are a common but poorly understood method of gene regulation, found in all kingdoms of life. These stretches of RNA transcripts change conformation after binding certain small target molecules, with consequences for gene control.

The anti-terminator was less thermodynamically stable than the terminator, and therefore much less likely to form. Because it formed slightly more quickly than the terminator, however, "it got its foot in the door," said Block.

"It's a bit like the old joke about escaping a bear in the woods," he said. "You don't actually have to run more quickly than the bear, you just have to run faster than your friend who's with you."

When the riboswitch's target molecule was present, the researchers found, the anti-terminator would consistently form, preventing the terminator from folding and allowing transcription to continue onward. The anti-terminator would only hold its shape for a second or so, but a second is just long enough.
"We were the first to actually see a riboswitch switch," Block said.

The team hopes to extend its techniques to other structured RNAs, including more riboswitches, as well as ribozymes – RNAs that can catalyze chemical reactions – and the tRNAs crucial to protein translation.

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 3,500+ scientific posters on ePosters
  • More Than 5,100+ 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

Water Dynamics Affect Coral Reefs
Understanding what aids or degrades these ecosystems can help focus conservation efforts on reefs that are most likely to survive global warming.
Monday, September 19, 2016
New Method of Cancer Immunotherapy
Stanford chemists have dicovered a new form of cancer immunotherapy using sugar presence manipulation.
Wednesday, August 24, 2016
Bone Marrow Transplants Without Using Chemotherapy
Scientists have devised a way to destroy blood stem cells in mice without using chemotherapy or radiotherapy, both of which have toxic side effects.
Friday, August 12, 2016
Mapping Antibody Creation in Humans
Researchers have created the first, detailed map of the body's antibody production, which could suggest new treatment options for immune disorders.
Wednesday, August 03, 2016
Rapidly Generating Bone, Heart Muscle
A new study shows that combining positive and negative signals can quickly and efficiently steer stem cells down complex developmental pathways to become specialized tissues that could be used in the clinic.
Saturday, July 23, 2016
New Treatment for Rare Blood Cancers
Drug called midostaurin showed promise in an international clinical trial led by a Stanford physician.
Wednesday, July 06, 2016
Guided Chemotherapy Missiles to Target Cancer Cells
Latching chemotherapy drugs onto proteins that seek out tumors could provide a new way of treating tumors in the brain or with limited blood supply that are hard to reach with traditional chemotherapy.
Tuesday, July 05, 2016
Link Between Canned Food, BPA Exposure Revealed
New Stanford research resolves the debate on the link between canned food and exposure to the hormone-disrupting chemical known as Bisphenol A, or BPA.
Friday, July 01, 2016
Guided Chemotherapy Missiles
Latching chemotherapy drugs onto proteins that seek out tumors could provide a new way of treating tumors in the brain or with limited blood supply that are hard to reach with traditional chemotherapy.
Monday, June 20, 2016
New Imaging Method Reveals Nanoscale Details about DNA
Enhancement to super-resolution microscopy shows orientation of individual molecules, providing a new window into DNA’s structure and dynamics.
Monday, June 20, 2016
$10M Grant Funds Infection-Focused Center
The new center will explore intracellular and intercellular processes by which salmonella bacteria, responsible for more than 100 million symptomatic infections annually, infect immune cells.
Wednesday, April 06, 2016
Resurrecting an Abandoned Drug
Previously discarded drug shows promise in helping human cells in a lab dish fight off two different viruses.
Wednesday, March 30, 2016
Fracking's Impact on Drinking Water Sources
A case study of a small Wyoming town reveals that practices common in the fracking industry may have widespread impacts on drinking water resources.
Wednesday, March 30, 2016
Imaging Cells and Tissues Under the Skin
First technique developed for viewing cells and tissues in three dimensions under the skin.
Tuesday, March 22, 2016
Glucose-Guzzling Immune Cells May Drive Coronary Artery Disease
Researchers at Stanford University have found excessive glucose uptake by inflammatory immune cells called macrophages, which reside in arterial plaques, may be behind coronary artery disease.
Wednesday, March 16, 2016
Scientific News
Integrated Omics Analysis
Studying multi-omics promises to give a more holistic picture of the organism and its place in its ecosystem, however despite the complexities involved those within the field are optimistic.
Unravelling the Role of Key Genes and DNA Methylation in Blood Cell Malignancies
Researchers from the University of Nebraska Medical Center have demonstrated the role of Dnmt3a in safeguarding normal haematopoiesis.
Salford Lung Study - The First Real World Clinical Trial
In this podcast, we learn about the Salford Lung Study and its potential to revolutionize the way we assess new drugs and treatments around the world.
Point of Care Diagnostics - A Cautious Revolution
Advances in molecular biology, coupled with the miniaturization and improved sensitivity of assays and devices in general, have enabled a new wave of point-of-care (POC) or “bedside” diagnostics.
Structure of Primary Cannabinoid Receptor is Revealed
The findings provide key insights into how natural and synthetic cannabinoids including tetrahydrocannabinol —a primary chemical in marijuana—bind at the CB1 receptor to produce their effects.
Overlooked Molecules Could Revolutionise our Understanding of the Immune System
Researchers have discovered that around one third of all the epitopes displayed for scanning by the immune system are a type known as ‘spliced’ epitopes.
Illumina Contributes to ClinVar Database
The contribution includes variants of all classifications, from pathogenic to benign, identified during interpretation of whole genome sequences generated in the CLIA-certified, CAP-accredited Illumina Clinical Services Laboratory.
Agilent Presents Early Career Professor Award to Dr. Roeland Verhaak
JAX professor recognized for the development and implementation of workflows for the analysis of big-data from transcriptomics to next generation sequencing approaches.
NIH Study Determines Key Differences between Allergic and Non-Allergic Dust Mite Proteins
Researchers at NIH have uncovered factors that lead to the development of dust mite allergy and assist in the design of better allergy therapies.
NIH Contributes to Global Effort to Prevent and Manage Lung Diseases
The large scale trial will measure health benefits of clean cookstoves.
Scroll Up
Scroll Down
Skyscraper Banner

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
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,100+ scientific videos