Featured Research

from universities, journals, and other organizations

'GPS system' for protein synthesis in nerve cells gives clues for understanding brain disorders

Date:
March 11, 2011
Source:
University of Pennsylvania School of Medicine
Summary:
Scientists can now explain how a class of RNA molecules is able to target the genetic building blocks that guide the functioning of a specific part of the nerve cell. Abnormalities at this site are in involved in epilepsy, neurodegenerative disease, and cognitive disorders.

Scientists at the University of Pennsylvania explain how a class of RNA molecules is able to target the genetic building blocks that guide the functioning of a specific part of the nerve cell. Abnormalities at this site are in involved in epilepsy, neurodegenerative disease, and cognitive disorders. Their results are published this week in the journal Neuron.

A team of researchers, led by James Eberwine, PhD, the Elmer Bobst Professor of Pharmacology in the School of Medicine, and Junhyong Kim, PhD, the Edmund J. and Louise W. Kahn Professor of Biology in the School of Arts and Sciences, looked at how RNA gets targeted to nerve cell dendrites, which branch from the cell body of the neuron and detect the electrical and chemical signals transmitted by the axons of other neurons. These studies were enabled through the use of sensitive single cell analysis techniques developed in the Eberwine lab.

They discovered a class of RNAs (called CIRTs) that have small regions of retained strings of genetic building blocks (introns). These special RNAs have the ability to home to the dendrite to guide protein synthesis there. Specifically, they found that the targeting ability of some CIRTs originates from retrotransposons, which are thought to come from viruses.

The team concentrated on one retained intron, a localized regulatory sequence called the ID element. "Targeting elements in general are used by cells to make sure RNAs get to where they ultimately need to go, the dendrite in the case of a neuron. "It's like a GPS system for an RNA within the cell," says co-first author Peter T. Buckley, PhD, a postdoctoral fellow in the Eberwine lab. "But it gets removed in the cytoplasm before protein synthesis occurs. That's why the ID sequence isn't seen in the final protein."

The intron is a guide for local control of gene expression. The team used a reporter gene in the ID element to track its movement from the nucleus to the dendrite.

"There are species to species differences in the proportion and type of retrotransposons that make up introns," explains co-first author Miler T. Lee, PhD, a postdoctoral fellow in Junhyong Kim's lab. For example, rats have 100,000 of these ID elements versus the 1,000 to 2,000 found in mice. "Our studies suggest that rats use this ID element to target mRNA to the dendrite while mice may use other localization mechanisms." These data suggest that researchers must be careful in selecting animal models for the study of neurological and psychiatry illnesses.

One of the ID elements the researchers identified and analyzed is in an intron present in the FMRI gene. Fragile X syndrome -- one of the most common causes of inherited mental retardation -- is caused by mutations in this gene. The gene encodes the FMRP protein, which controls the availability of select proteins involved in neuron-to-neuron communication. The ID element in the FMR1 mRNA, in part, targets the RNA to where the FMRP protein is synthesized, which in turn controls how and where other proteins are made.

Because some retrotransposons are derived from viruses these data provide a mechanism by which normal cell functioning could be altered by viral infection. Upon infection of cells by viruses cellular proteins are often hijacked to permit the virus to function and divide. Since some RNAs that are involved in learning and memory contain ID sequences very similar to viruses, perhaps the proteins that move the RNAs to the dendrite are hijacked by an invading virus, surmise the researchers. The result being that the normal cell RNA does not move to its proper cellular position. If this happens during a critical period of development proper neuronal connectivity may be compromised and could result in long-term dysfunction of the central nervous system. This research area is currently under active investigation in the Eberwine and Kim labs.

These intron sequences have previously been thought to be junk RNA with no function, yet as shown in this study -- in some cases -- introns are functional outside of the nucleus. Extensive bioinformatic analysis performed by the team also suggests other functions including the possibility that outside of the nucleus retained introns may produce small RNAs that could regulate other RNAs.

The teams are now looking into perturbing this intricate system to see if they can change RNA targeting, as well as translation and protein function.

Other members of the teams are Jai-Yoon Sul, Kevin Miyashiro, Thomas Bell, and Stephen Fisher. This work was funded by HRF funds from the Commonwealth of Pennsylvania and the National Institutes of Mental Health and National Institute, and the Director's Fund of the National Institutes of Health.


Story Source:

The above story is based on materials provided by University of Pennsylvania School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Peter T. Buckley, Miler T. Lee, Jai-Yoon Sul, Kevin Y. Miyashiro, Thomas J. Bell, Stephen A. Fisher, Junhyong Kim, James Eberwine. Cytoplasmic Intron Sequence-Retaining Transcripts Can Be Dendritically Targeted via ID Element Retrotransposons. Neuron, Volume 69, Issue 5, 877-884, 10 March 2011 DOI: 10.1016/j.neuron.2011.02.028

Cite This Page:

University of Pennsylvania School of Medicine. "'GPS system' for protein synthesis in nerve cells gives clues for understanding brain disorders." ScienceDaily. ScienceDaily, 11 March 2011. <www.sciencedaily.com/releases/2011/03/110309125149.htm>.
University of Pennsylvania School of Medicine. (2011, March 11). 'GPS system' for protein synthesis in nerve cells gives clues for understanding brain disorders. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2011/03/110309125149.htm
University of Pennsylvania School of Medicine. "'GPS system' for protein synthesis in nerve cells gives clues for understanding brain disorders." ScienceDaily. www.sciencedaily.com/releases/2011/03/110309125149.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com
West Africa Gripped by Deadly Ebola Outbreak

West Africa Gripped by Deadly Ebola Outbreak

AFP (July 28, 2014) The worst-ever outbreak of the deadly Ebola epidemic grips west Africa, killing hundreds. Duration: 00:48 Video provided by AFP
Powered by NewsLook.com
Trees Could Save More Than 850 Lives Each Year

Trees Could Save More Than 850 Lives Each Year

Newsy (July 27, 2014) A national study conducted by the USDA Forest Service found that trees collectively save more than 850 lives on an annual basis. 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:
from the past week

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