Featured Research

from universities, journals, and other organizations

Language of RNA decoded: Study reveals new function for pseudogenes and noncoding RNAs

Date:
June 24, 2010
Source:
Beth Israel Deaconess Medical Center
Summary:
The central dogma of molecular biology holds that genetic information is transferred from DNA to functional proteins by way of messenger RNA (mRNA). This suggests that mRNA has but a single role, that being to encode for proteins. Now, a cancer genetics team suggests there is much more to RNA than meets the eye.

The central dogma of molecular biology, as proposed in 1970 by Francis Crick and James Watson, holds that genetic information is transferred from DNA to functional proteins by way of messenger RNA (mRNA). This suggests that mRNA has but a single role, that being to encode for proteins.

Now, a cancer genetics team at Beth Israel Deaconess Medical Center (BIDMC) suggests there is much more to RNA than meets the eye.

In a study appearing in the June 24, 2010 issue of Nature, the authors describe a new regulatory role for RNA -- independent of their protein-coding function -- that relies on their ability to communicate with one another. Of potentially even greater significance, because this new function also holds true for thousands of noncoding RNAs, the discovery dramatically increases the known pool of functional genetic information.

The new findings suggest that nature has crafted a clever tale of espionage such that thousands upon thousands of mRNAs and noncoding RNAs, together with a mysterious group of genetic relics known as pseudogenes, take part in undercover reconnaissance of cellular microRNAs, resulting in a new category of genetic elements which, when mutated, can have consequences for cancer and human disease at large.

"Because this new function does not depend on the blueprint that RNAs harbor in their protein-encoding nucleotide sequence, the discovery additionally holds true for the thousands of noncoding RNA molecules in the cell," explains senior author Pier Paolo Pandolfi, MD, PhD, Director of Research at the BIDMC Cancer Center and George C. Reisman Professor of Medicine at Harvard Medical School."This means that not only have we discovered a new language for mRNA, but we have also translated the previously unknown language of up to 17,000 pseudogenes and at least 10,000 long non-coding (lnc) RNAs. Consequently, we now know the function of an estimated 30,000 new entities, offering a novel dimension by which cellular and tumor biology can be regulated, and effectively doubling the size of the functional genome."

MicroRNAs are small RNA molecules that repress the expression levels of numerous genes by binding to mRNA, thereby preventing it from delivering its protein coding message. As a result, microRNAs are known to have a hand in human diseases, including cancer.

But, the Pandolfi team thought that RNA might be taking a different tactic. "Although it is conventional knowledge that microRNA can block mRNA function, we suspected that the roles of microRNA and mRNA were actually flipped," explains Pandolfi. "In other words, instead of microRNA binding to mRNA, we thought that RNAs were actually sequestering the microRNAs, thereby protecting mRNA and rendering the microRNAs ineffective on their other targets."

And, indeed this proved to be the case. The authors coined the term "competitive endogenous RNAs" or "ceRNAs" to describe this new RNA activity.

To further test their hypothesis, the scientists turned to pseudogenes, a group of "genetic relics" that do not encode for proteins. Since pseudogenes are more or less identical to their ancestral genes, the authors knew they would be the perfect "combatants" because they would both recognize and compete for the same group of microRNAs as their ancestral genes.

The scientists studied the interaction between the RNA encoding for the PTEN tumor suppressor gene and its closely related pseudogene, PTENP1. Through this new mechanism, they were able to demonstrate that PTENP1 also acts as a tumor suppressor. They also proved this to be true for the KRAS oncogene and its pseudogene KRAS1P; in this case the pseudogene was acting as a new oncogene.

"We now understand how these RNA units talk with one another," says Pandolfi. "Because all RNA molecules are competing to be heard, it had been difficult to tease out the messages amid the noise. But now that we know what to listen for, we can computationally predict which RNA can act as a ceRNA and what that ceRNA can do. And we can apply these findings to any RNA molecule.

"We have identified PTENP1 and KRAS1P as well as several thousand other uncharacterized RNA molecules as potential new factors contributing to human disease," he adds. "These findings help define a new fundamental biological dimension that we hope will allow for the rapid identification and functional characterizations of new disease-related genes including cancer, thereby improving diagnosis and effective therapy."

This study was supported, in part, by a grant from the National Institutes of Health, as well as fellowship support from the Istituto Toscano Tumori, the American Italian Cancer Foundation, the Human Frontier Science Program and the Canadian Institutes of Health Research.

Coauthors include Laura Poliseno and Leonardo Salmena (co-first authors) and William Haveman, all of BIDMC; Jiangwen Zhang of the Center for Systems Biology at Harvard University; and Brett Carver of Memorial Sloan-Kettering Cancer Center.


Story Source:

The above story is based on materials provided by Beth Israel Deaconess Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Beth Israel Deaconess Medical Center. "Language of RNA decoded: Study reveals new function for pseudogenes and noncoding RNAs." ScienceDaily. ScienceDaily, 24 June 2010. <www.sciencedaily.com/releases/2010/06/100623132102.htm>.
Beth Israel Deaconess Medical Center. (2010, June 24). Language of RNA decoded: Study reveals new function for pseudogenes and noncoding RNAs. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2010/06/100623132102.htm
Beth Israel Deaconess Medical Center. "Language of RNA decoded: Study reveals new function for pseudogenes and noncoding RNAs." ScienceDaily. www.sciencedaily.com/releases/2010/06/100623132102.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Fears Keep Guinea Hospitals Empty

Ebola Fears Keep Guinea Hospitals Empty

AP (Oct. 23, 2014) Fears of Ebola are keeping doctors and patients alike away from hospitals in the West African nation of Guinea. (Oct. 23) Video provided by AP
Powered by NewsLook.com
Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
More People Diagnosed With TB In 2013, But There's Good News

More People Diagnosed With TB In 2013, But There's Good News

Newsy (Oct. 22, 2014) The World Health Organizations says TB numbers rose in 2013, but it's partly due to better detection and more survivors. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins