Featured Research

from universities, journals, and other organizations

Mutation causing neurodegeneration discovered

Date:
January 19, 2012
Source:
Jackson Laboratory
Summary:
Scientists have discovered a defect in the RNA splicing process in neurons that may contribute to neurological disease. The researchers found that a mutation in just one of the many copies of a gene known as U2 snRNAs, which is involved in the intricate processing of protein-encoding RNAs, causes neurodegeneration.

A Jackson Laboratory research team led by Professor and Howard Hughes Medical Investigator Susan Ackerman, Ph.D., has discovered a defect in the RNA splicing process in neurons that may contribute to neurological disease.

Related Articles


The researchers found that a mutation in just one of the many copies of a gene known as U2 snRNAs, which is involved in the intricate processing of protein-encoding RNAs, causes neurodegeneration.

Many so-called non-coding RNAs -- those that don't directly encode proteins -- are found in multiple copies in the genome, Ackerman says. "These copies are identical, or nearly identical, so conventional wisdom suggested they were redundant. For the first time, we show that a mutation in one copy can lead to disease."

The results, published in the journal Cell, suggest that disease-causing mutations may exist among other repetitive genes. "This opens up a whole new way of studying these RNAs," Ackerman notes, "including the types of disruptions in RNA processing that can lead to degeneration."

Neurons, like most other cells, build the workhorse proteins that carry out vital functions from the genetic "blueprint" encoded in DNA. In broad strokes, DNA gets copied by pre-messenger RNA (pre-mRNA), then pre-mRNA undergoes a splicing process before transporting the genetic code to the ribosome, where proteins are manufactured. But there's much more to it than that.

Specialized RNAs called U-snRNAs are essential to the splicing process. U-snRNAs are highly conserved, meaning that they are found all along the evolutionary pathway from simple organisms to humans. Ackerman showed that mutations in one form of snRNA, known as U2, lead to movement problems and early neuron death in mice.

U2 is a repetitive gene, meaning there are many copies of the same sequence. A mutation in just one copy led to the observed disorders by disrupting alternative splicing events, part of the splicing process that normally allows the creation of two or more protein forms from the same stretch of pre-mRNA.

The error leads to production of mRNAs containing regions known as introns that should have been removed. These abnormal mRNAs cause cell death, either through active toxicity or the production of dysfunctional proteins. Moreover, the researchers noted that the severity of the splicing abnormalities and cell death depend on the "dosage" level of the mutant gene.

Also, Ackerman and her lab noted that the highest levels of the mutant U2 were found in the cerebellum of the brain, indicating that the expression of mammalian U2s, previously thought to be universal, may be different among various cell types.

The Jackson Laboratory is an independent, nonprofit biomedical research institution and National Cancer Institute-designated Cancer Center based in Bar Harbor, Maine, with a facility in Sacramento, Calif., and a total staff of about 1,400. Its mission is to discover the genetic basis for preventing, treating and curing human disease, and to enable research and education for the global biomedical community.


Story Source:

The above story is based on materials provided by Jackson Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yichang Jia, JohnC. Mu, SusanL. Ackerman. Mutation of a U2 snRNA Gene Causes Global Disruption of Alternative Splicing and Neurodegeneration. Cell, 2012; 148 (1-2): 296 DOI: 10.1016/j.cell.2011.11.057

Cite This Page:

Jackson Laboratory. "Mutation causing neurodegeneration discovered." ScienceDaily. ScienceDaily, 19 January 2012. <www.sciencedaily.com/releases/2012/01/120119133603.htm>.
Jackson Laboratory. (2012, January 19). Mutation causing neurodegeneration discovered. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2012/01/120119133603.htm
Jackson Laboratory. "Mutation causing neurodegeneration discovered." ScienceDaily. www.sciencedaily.com/releases/2012/01/120119133603.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
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