Navigation Links
Wistar researchers discover new class of objects encoded within the genome
Date:10/6/2010

Despite progress in decoding the genome, scientists estimate that fully 95 percent of our DNA represents dark, unknown territory. In the October 1 issue of the journal Cell researchers at The Wistar Institute shed new light on the genetic unknown with the discovery of the ability of long non-coding RNA (ncRNA) to promote gene expression. The researchers believe these long ncRNA molecules may represent so-called gene enhancer elementsshort regions of DNA that can increase gene transcription. While scientists have known about gene enhancers for decades, there has been no consensus about how these enhancers work.

These findings join a growing body of evidence that the classic "central dogma" of genetics is incomplete. In the central dogma, chromosomal DNA is transcribed into RNA, which is then translated by the cell into proteins. In recent years, however, scientists have found that not all transcribed RNA molecules become translated into proteins. In fact, studies have shown that whole swathes of the genome are transcribed for unknown reasons.

In the present study, the Wistar researchers pinpoint 3,000 long ncRNAs and estimate that there could be a total of between 10,000 to 12,000 long ncRNA sequences within our DNA. This number is comparable to the 20,000 genes that are known to encode proteins. Most long ncRNAs are encoded in DNA near genes known to be important to both stem cells and cancer. This observation also suggests that targeting ncRNAs may represent a new strategy in slowing cancer growth.

"We are excited, first of all, because this is a new discovery about the very nature of human DNA; a new class of genetic object and a new layer of genetic regulation," said Ramin Shiekhattar, Ph.D., Wistar's Herbert Kean, M.D., Family Professor and senior author of the study.

"Secondly, we may have solved, in part, a great mystery in modern genetics. These long non-coding RNA sequences may account for the activity of enhancer elements, which have been well-studied but never quite characterized," Shiekhattar said.

Almost three years ago, while at the Centre for Genomic Regulation in Barcelona, Spain, Shiekhattar began a prospective hunt for non-coding RNA sequences using GENCODE, a database that annotates the human genome with currently available scientific evidence. After filtering out protein-coding transcripts and non-coding RNAs that might overlap known protein-coding genes, they found approximately 3,000 long ncRNA sequences. At the time, GENCODE only accounted for a third of the genome, so Shiekhattar estimates that there are likely more.

The researchers mapped the ncRNA sites within the genome, and found that ncRNAs tended to be located near genes that influence how stem cells change into other cell types. Shiekhattar and his colleagues then developed new assays to screen cell cultures for these ncRNA sequences, and discovered that ncRNAs were found extensively in a variety of cell types.

The idea that molecules of RNA can have a DNA-regulating effect is well established. More than 1,000 so-called microRNAs are known to science, for example, and their effect on silencing genes has been well described. According to Shiekhattar, he assumed that long ncRNAs would also silence genes, not promote their activation. To his surprise, the researchers found that depleting a cell of ncRNAs actually decreased the degree of overall gene expression of neighboring genes, revealing a role for ncRNAs in potentiating gene expression.

In fact, when Shiekhattar and his colleagues depleted adult stem cells of a specific long ncRNA, known as ncRNA-activating 7 (ncRNA-a7), it had the same effect as depleting the protein product of a nearby gene, Snai1, which regulates how the cells migrate. Their studies further showed that inserting an ncRNA next to a gene for luciferasethe enzyme responsible for a firefly's glowincreased the amount of protein produced by that gene in cells grown in culture. While not all long ncRNAs may act like enhancers, the majority of the ones the team studied do, Shiekhattar says.

"We know long non-coding RNAs can promote gene expression, but what we need to know now is how they do it," Shiekhattar said, "which is precisely the object of our ongoing research plan."


'/>"/>

Contact: Greg Lester
glester@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert

Related medicine news :

1. Wistar scientists explain the persistence of melanoma through dynamic stemness
2. Blood test could diagnose Alzheimers disease, UT Southwestern researchers find
3. Mayo researchers find biomarkers for personalizing radiation cancer treatment
4. Insurance, Race and Poverty Affect Cancer Care, Researchers Report
5. Johns Hopkins researchers turn off severe food allergies in mice
6. UTHealth researchers awarded $15 million for teen pregnancy prevention
7. Researchers discover genetic changes that make some forms of brain cancer more aggressive
8. Researchers find no difference in drugs for macular degeneration
9. Researchers advance biosynthesis of potent anti-cancer drug Taxol
10. Researchers engineer microbes for low-cost production of anti-cancer drug, Taxol
11. Researchers at the University of Granada associate trigger points with shoulder injury
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... , ... June 25, 2016 , ... On Friday, June ... a Bronze Wellness at Work award to iHire in recognition of their exemplary accomplishments ... of the 7th annual Maryland Workplace Health & Wellness Symposium at the BWI Marriott ...
(Date:6/24/2016)... Marne, Michigan (PRWEB) , ... June 24, 2016 , ... ... awareness about the dangers associated with chronic pain and the benefits of holistic treatments, ... for individuals who are suffering with Sickle Cell Disease. , Sickle Cell Disease (SCD) ...
(Date:6/24/2016)... ... June 24, 2016 , ... Dr. Amanda ... orthodontic treatment. Dr. Cheng has extensive experience with all areas of orthodontics, including ... accelerated osteogenic orthodontics. , Micro-osteoperforation is a revolutionary adjunct to orthodontic treatment. ...
(Date:6/24/2016)... ... June 24, 2016 , ... EB ... Decision Making in Emergency Medicine conference in Ponte Vedra Beach, FL. The awards ... in Emergency Medicine Practice and Pediatric Emergency Medicine Practice. , “With ...
(Date:6/24/2016)... ... , ... National recruitment firm Slone Partners is pleased to announce ... experience, as Vice President of North American Capital Sales at HTG Molecular . ... sales team in the commercialization of the HTG EdgeSeq system and associated reagents in ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... NAMUR , Belgium , ...  (NYSE MKT: VNRX), today announced the appointment of ... Board of Directors as a Non-Executive Director, effective ... the Company,s Audit, Compensation and Nominations and Governance ... Board, Dr. Futcher will provide independent expertise and ...
(Date:6/23/2016)... 2016 Any dentist who has made an implant ... process. Many of them do not even offer this as ... high laboratory costs involved. And those who ARE able to ... a high cost that the majority of today,s patients would ... Parsa Zadeh , founder of Dental Evolutions Inc. and inventor ...
(Date:6/23/2016)... DUBLIN , June 23, 2016 ... "Global MEMS Devices Medical Market Analysis 2016 - Forecast to ... The report contains up to date financial ... reliable analysis. Assessment of major trends with potential impact on ... dive analysis of market segmentation which comprises of sub markets, ...
Breaking Medicine Technology: