Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
>
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

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

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 3,300+ scientific posters on ePosters
  • More than 4,900+ 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

Transcription Factor Isoforms Implicated in Colon Diseases
UC Riverside study explains how distribution of two forms of a transcription factor in the colon influence risk of disease.
Thursday, May 19, 2016
Cat Stem Cell Therapy Gives Humans Hope
By the time Bob the cat came to the UC Davis veterinary hospital, he had used up most of his nine lives.
Monday, February 08, 2016
Embryonic Switch for Cancer Stem Cell Generation
An international team of scientists report that decreases in a specific group of proteins trigger changes in the cancer microenvironment that accelerate growth and development of therapy-resistant cancer stem cells (CSCs).
Wednesday, December 02, 2015
Artificial Kidney Research Gets A Boost
Development of a surgically implantable, artificial kidney — a promising alternative to kidney transplantation or dialysis for people with end-stage kidney disease — has received a $6 million boost.
Monday, November 09, 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
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
Grant Supports Creation of Patient-Derived Stem Cell Lines
Researchers have received a two-year, $600,000 grant from the National Institute on Aging to develop and study patient-derived stem cell lines.
Thursday, December 12, 2013
Prostate Cancer Stem Cells are a Moving Target
Researchers have discovered how prostate cancer stem cells evolve as the disease progresses, a finding that could help point the way to more highly targeted therapies.
Friday, December 06, 2013
Researchers Change Cell Types by Flipping a Single Switch
New findings have identified a method for changing one cell type into another in a process called forced transdifferentiation.
Friday, December 06, 2013
Understanding a Protein’s Role in Familial Alzheimer’s
Researchers have used genetic engineering of human iPSC’s to specifically and precisely parse the roles of a key mutated protein in causing familial Alzheimer's disease (AD).
Monday, November 18, 2013
$100M gift launches Sanford Stem Cell Clinical Center
T. Denny Sanford has committed $100 million to the creation of the Sanford Stem Cell Clinical Center at the University of California, San Diego.
Wednesday, November 06, 2013
Grafted Limb Cells Acquire Molecular ‘Fingerprint’ of New Location
Findings further creation of regenerative therapies for humans.
Wednesday, October 30, 2013
From Mature Cells to Embryonic-Like Stem Cells
Bioengineers have shown that physical cues can replace certain chemicals when nudging mature cells back to a pluripotent stage.
Tuesday, October 22, 2013
Researchers Develop Stem Cell Therapies for Acute Lung Injury
An estimated 200,000 patients a year have acute respiratory failure in the U.S. and mortality is about 30 to 40 percent.
Monday, October 21, 2013
Single Gene Mutation Linked to Neurological Disorders
Mutation could offer insights into Alzheimer’s, Parkinson’s and Huntigton’s Diseases.
Wednesday, October 16, 2013
Scientific News
Genetic Variability in Cell Bank Lots
Researchers working with cancer cells from the same cell bank acquired at the same time, found that the cells were genetically different.
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.
New Therapeutic Targets For Small Cell Lung Cancer Identified
Researchers at UTSW Medical Center have identified a protein termed ASCL1 that is essential to the development of small cell lung cancer.
New Mechanism of Tuberculosis Infection
Researchers have identified a new infection mechanism of tuberculosis that could lead to a new therapeutic angle.
Modelling ALS Requires ‘Aged’ Stem Cells
Research suggests engineered cells are too ‘young’ to accurately model ALS and should be 'aged' to speed progress toward finding potential treatments.
Protein Reinforces Growth of Damaged Muscles
Biologists have found a protein involved in stem cells that bolsters damaged muscle tissue growth - potential for muscle degeneration treatments.
Treating HIV with Cancer-Fighting Gene Shows Promise
A type of gene immunotherapy that has shown promising results against cancer could also be used against HIV.
'Antigen-Presenting Cell' Defends Against Cancer
Through advanced imaging, researchers have identified cells that encourages increases in immune system cancer defences.
HIV Hides No Longer
Researchers are working to create proteins that clear HIV-infected cells in order to eliminate latent infection and dormancy.
R&D Agreement for Development of CtDNA Diagnostics
SeraCare and NIST partner for development of ctDNA diagnostic assay reference materials.
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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!