Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
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 2,900+ scientific posters on ePosters
  • More Than 4,200+ 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

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
Crowdfunding the Fight Against Cancer
From budding social causes to groundbreaking businesses to the next big band, crowdfunding has helped connect countless worthy projects with like-minded people willing to support their efforts, even in small ways. But could crowdfunding help fight cancer?
Monday, February 08, 2016
Toxic Pollutants Found in Fish Across the World's Oceans
Scripps researchers' analysis shows highly variable pollutant concentrations in fish meat.
Friday, January 29, 2016
Key Enzyme in Pierce’s Disease Grapevine Damage Uncovered
UC Davis plant scientists have identified an enzyme that appears to play a key role in the insect-transmitted bacterial infection of grapevines with Pierce’s disease, which annually costs California’s grape and wine industries more than $100 million.
Wednesday, January 13, 2016
Science Magazine Names CRISPR ‘Breakthrough of the Year’
In its year-end issue, the journal Science chose the CRISPR genome-editing technology invented at UC Berkeley 2015’s Breakthrough of the Year.
Monday, December 21, 2015
Genome Sequencing May Save California's Legendary Sugar Pine
The genome of California’s legendary sugar pine, which naturalist John Muir declared to be “king of the conifers” more than a century ago, has been sequenced by a research team led by UC Davis scientists.
Thursday, December 17, 2015
Cellular “ORACLs” to Aid Drug Discovery
New approach for finding therapeutics is inspired by face-recognition software.
Wednesday, December 16, 2015
New Virus Disovered, Linked To Hepatitis C
Study is first to reveal entire genetic makeup of human pegivirus 2.
Tuesday, December 15, 2015
CRISPR-Cas9 Helps Uncover Genetics of Exotic Organisms
A new study illustrates the ease with which CRISPR-Cas9 can knock out genes in exotic animals to learn how those genes control growth and development.
Friday, December 11, 2015
UC Davis Cracks the Walnut Genome
Scientists at the University of California, Davis, have for the first time sequenced the genome of a commercial walnut variety.
Friday, December 11, 2015
‘Purity’ Of Tumor Samples May Significantly Bias Genomic Analyses
Non-cancerous tumor components influence research findings, clinical classifications, study shows.
Monday, December 07, 2015
New Method for Screening Cancer Cells
Parallel microfiltration could lead to better treatments for a number of diseases, UCLA-led study says.
Thursday, December 03, 2015
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
New Organic Plant Breeding Effort Launched
A new effort to provide California growers with seeds for tomato, bean, pepper and other crop varieties that are specially bred for organic farming has been launched at UC Davis.
Tuesday, December 01, 2015
When it Comes to Breast Cancer, Common Pigeon is No Bird Brain
If pigeons went to medical school and specialized in pathology or radiology, they’d be pretty good at distinguishing digitized microscope slides and mammograms of normal vs. cancerous breast tissue, a new study has found.
Monday, November 30, 2015
Scientific News
Retractable Protein Nanoneedles
The ability to control the transfer of molecules through cellular membranes is an important function in synthetic biology; a new study from researchers at Harvard’s Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS) introduces a novel mechanical method for controlling release of molecules inside cells.
Leukemia’s Surroundings Key to its Growth
Researchers at The University of Texas at Austin have discovered that a type of cancer found primarily in children can grow only when signaled to do so by other nearby cells that are noncancerous.
Common Cell Transformed into Master Heart Cell
By genetically reprogramming the most common type of cell in mammalian connective tissue, researchers at the University of Wisconsin—Madison have generated master heart cells — primitive progenitors that form the developing heart.
‘Smelling’ Prostate Cancer
A research team from the University of Liverpool and the University of the West of England (UWE Bristol) has reached an important milestone towards creating a urine diagnostic test for prostate cancer that could mean that invasive diagnostic procedures that men currently undergo eventually become a thing of the past.
Genetic Mutation that Prevents Diabetes Complications
The most significant complications of diabetes include diabetic retinal disease, or retinopathy, and diabetic kidney disease, or nephropathy. Both involve damaged capillaries.
A Crystal Clear View of Biomolecules
Fundamental discovery triggers paradigm shift in crystallography.
Could the Food we Eat Affect Our Genes?
Almost all of our genes may be influenced by the food we eat, according to new research.
NIH Seeks Research Applications to Study Zika in Pregnancy, Developing Fetus
Institute has announced that the new effort seeks to understand virus effect on reproduction and child development.
Iron in the Blood Could Cause Cell Damage
Concentrations of iron similar to those delivered through standard treatments can trigger DNA damage within 10 minutes, when given to cells in the laboratory.
Criminal Justice Alcohol Program Linked to Decreased Mortality
Institute has announced that in the criminal justice alcohol program deaths dropped by 4.2 percent over six years.
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
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!