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

Researchers Un-Junking Junk DNA

Published: Wednesday, November 13, 2013
Last Updated: Wednesday, November 13, 2013
Bookmark and Share
A study shines a new light on molecular tools our cells use to govern regulated gene expression.

The study will be published online in advance of print Nov. 10 in the journal Nature Structural and Molecular Biology.

"We uncovered a novel mechanism that allows proteins that direct pre-mRNA splicing — RNA-binding proteins — to induce a regulatory effect from greater distances than was thought possible," said first author Michael T. Lovci, a biomedical sciences graduate student working in the Department of Cellular and Molecular Medicine, the Stem Cell Research Program and Institute for Genomic Medicine at UC San Diego.

Researchers from California, Oregon, Singapore and Brazil made this finding while working toward an understanding of the most basic signals that direct cell function. According to Lovci, the work broadens the scope that future studies on the topic must consider. More importantly, it expands potential targets of rationally designed therapies which could correct molecular defects through antisense RNA oligonucleotides — small pieces of DNA or RNA that can bind to specific RNA targets to either block interactions with RNA-binding proteins and/or initiate degradation of the target RNA.

"This study provides answers for a decade-old question in biology," explained principal investigator Gene W. Yeo, PhD, assistant professor of Cellular and Molecular Medicine, member of the Stem Cell Research Program and Institute for Genomic Medicine at UC San Diego, as well as with National University of Singapore. "When the sequence of the human genome just over a decade ago, we learned that less than 3 percent of the entire genome contains information that encodes for proteins. This posed a difficult problem for genome scientists - what is the other 97 percent doing?"

The role of the rest of the genome was largely a mystery and was thus referred to as "junk DNA." Since then sequencing of other, non-human, genomes has allowed scientists to delineate the sequences in the genome that are remarkably preserved across hundreds of millions of years of evolution. It is widely accepted that this evidence of evolutionary constraint implies that, even without coding for protein, certain segments of the genome are vital for life and development.

Using this evolutionary conservation as a benchmark, scientists have described varied ways cells use these non-protein-coding regions. For instance, some exist to serve as DNA docking sites for proteins which activate or repress RNA transcription. Others, which were the focus of this study, regulate alternative mRNA splicing.

Eukaryotic cells use alternative pre-mRNA splicing to generate protein diversity in development and in response to the environment. By selectively including or excluding regions of pre-mRNAs, cells make on average ten versions of each of the more than 20,000 genes in the genome. RNA-binding proteins are the class of proteins most closely linked to these decisions, but very little is known about how they actually perform their roles in cells.

"For most genes, protein-coding space is distributed in segments on the scale of islands in an ocean," said John G. Conboy, PhD, of the Lawrence Berkeley National Laboratory, co-lead investigator on the study. "RNA processing machinery, including RNA-binding proteins, must pick out these small portions and accurately splice them together to make functional proteins. Our work shows that not only is the sequence space nearby these ‘islands' important for gene regulation, but that evolutionarily conserved sequences very far away from these islands are important for coordinating splicing decisions."

Since this premise defies existing models for alternative splicing regulation, whereby regulation is enacted very close to protein-coding segments, the authors sought to define the mechanism by which long-range splicing regulation can occur. They identified RNA structures — RNA that is folded and base-paired upon itself — that exist between regulatory sites and far-away protein-coding "islands." Dubbing these types of interactions "RNA-bridges" for their capacity to link distant regulators to their targets, the authors show that this is likely a common and under-appreciated mechanism for regulation of alternative splicing.

These findings have foreseeable implications in the study of biomedicine, the researchers said, as the RNA-binding proteins on which they focused — RBFOX1 and RBFOX2 — show strong associations with neurodevelopmental disorders such as autism and also certain cancers. Since these two proteins act upstream of a cascade of effects, understanding how they guide alternative splicing decisions may lead to advancements in targeted therapies which correct the inappropriate splicing decisions that underlie many diseases.

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 2,600+ scientific posters on ePosters
  • More Than 3,800+ 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

New Autism Genes Are Revealed in Largest-Ever Study
Work draws more detailed picture of genetic risk, sheds light on sex differences in diagnosis.
Wednesday, September 30, 2015
Influenza A Viruses More Likely To Emerge In East Asia Than North America
Novel strains of influenza A are more likely to emerge in East Asia than in North America, according to a global analysis by the One Health Institute at the UC Davis School of Veterinary Medicine and EcoHealth Alliance.
Wednesday, September 30, 2015
Opening the Door to Safer, More Precise Cancer Therapies
New method regulates when, and how strongly, cancer-killing therapeutic T cells are activated.
Tuesday, September 29, 2015
Crunching Numbers to Combat Cancer
UCSF receives $5 million to integrate data from cancer research models.
Wednesday, September 16, 2015
Virus In Cattle Linked To Human Breast Cancer
A new study by UC Berkeley researchers establishes for the first time a link between infection with the bovine leukemia virus and human breast cancer.
Wednesday, September 16, 2015
Ultrafast DNA Diagnostics
New technology developed by UC Berkeley bioengineers promises to make a workhorse lab tool cheaper, more portable and many times faster by accelerating the heating and cooling of genetic samples with the switch of a light.
Monday, August 03, 2015
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Tuesday, July 28, 2015
Simple Technology Makes CRISPR Gene Editing Cheaper
University of California, Berkeley, researchers have discovered a much cheaper and easier way to target a hot new gene editing tool, CRISPR-Cas9, to cut or label DNA.
Friday, July 24, 2015
Printed "Smart Cap" Detects Spoiled Food
It might not be long before consumers can just hit “print” to create an electronic circuit or wireless sensor in the comfort of their homes.
Tuesday, July 21, 2015
Growing Spinal Disc Tissue
Scientists develop new method for growing spinal disc tissue in the lab for combating chronic back pain.
Friday, July 03, 2015
Delivering Drugs to the Right Place
Thomas Weimbs has developed a targeted drug delivery method that could potentially slow the progression of polycystic kidney disease.
Monday, June 29, 2015
The Deep Carbon Cycle
Over billions of years, the total carbon content of the outer part of the Earth—in its upper mantle, crust, oceans and atmospheres—has gradually increased, scientists report.
Tuesday, June 23, 2015
Designing New Pain Relief Drugs
Researchers have identified the molecular interactions that allow capsaicin to activate the body’s primary receptor for sensing heat and pain, paving the way for the design of more selective and effective drugs to relieve pain.
Thursday, June 11, 2015
Engineers Crack DNA Code of Autoimmune Disorders
Researchers have identified an unexpectedly general set of rules that determine which molecules can cause the immune system to become vulnerable to the autoimmune disorders lupus and psoriasis.
Wednesday, June 10, 2015
Genetic Markers for Detecting and Treating Ovarian Cancer
Custom bioinformatics algorithm identifies human mRNAs that distinguish ovarian cancer cells from normal cells and provide new therapeutic targets
Wednesday, May 27, 2015
Scientific News
13 Ways to Stop an Unseen Force from Disrupting Weighing
Download a free Mettler Toledo paper to discover how to halt static’s negative effects before the next weigh-in.
Flinders Ig Nobel Winner Cracks Global Anaesthetic
One of the world’s most in-demand anaesthetics can now be produced on the spot, thanks to the thermos-flask sized device that recently won Flinders University inventor Professor Colin Raston an Ig Nobel prize.
Resurrected Proteins Double Their Natural Activity
Researchers demonstrate method for reviving denatured proteins.
Genes That Protect African Children From Developing Malaria Identified
Variations in DNA at a specific location on the genome that protect African children from developing severe malaria, in some cases nearly halving a child’s chance of developing the life-threatening disease, have been identified in the largest genetic association study of malaria to date.
Messing With The Monsoon
Manmade aerosols can alter rainfall in the world’s most populous region.
Potential Target for Treatment of Autism
Grant of $2.4 million will support further research.
Scientists Decode Structure at Root of Muscular Disease
Researchers at Rice University and Baylor College of Medicine have unlocked the structural details of a protein seen as key to treating a neuromuscular disease.
Sniffing Out Cancer
Scientists have been exploring new ways to “smell” signs of cancer by analyzing what’s in patients’ breath.
New Test Detects All Viruses
A new test detects virtually any virus that infects people and animals, according to research at Washington University School of Medicine in St. Louis, where the technology was developed.
Inroads Against Leukemia
Potential for halting disease in molecule isolated from sea sponges.
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
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos