Featured Research

from universities, journals, and other organizations

Molecular Basis Of Leading Genetic Cause Of Infant Death Discovered

Date:
November 26, 1998
Source:
University Of Pennsylvania Medical Center
Summary:
Understanding how genetic information is translated, via messenger RNA (mRNA), to correctly construct proteins has profound clinical and basic research implications. Researchers at the University of Pennsylvania Medical Center have now found a link between this basic biological process and spinal muscular atrophy, the leading genetic cause of infant death.

Understanding how genetic information is translated, via messenger RNA (mRNA), to correctly construct proteins has profound clinical and basic research implications. Researchers at the University of Pennsylvania Medical Center have now found a link between this basic biological process and spinal muscular atrophy, the leading genetic cause of infant death. This neuromuscular disease, characterized by the degeneration of motor nerve cells that control the body's involuntary muscles from the head down, originates from defects in the Survival of Motor Neuron (SMN) gene on chromosome 5. Spinal muscle atrophy is an inherited condition that affects about one in 6,000.

"Our work describes the function of the SMN protein and links it to spinal muscle atrophy, opening up the possibility to search for therapeutics," reports Gideon Dreyfuss, Ph.D., the Isaac Norris professor of biochemistry and biophysics and a Howard Hughes Medical Institute investigator. Reduced levels or mutations in the SMN protein lead to spinal muscle atrophy. Dreyfuss and his colleagues -- Penn researchers Livio Pellizzoni, Bernard Charroux, and Naoyuki Kataoka -- discovered that SMN has a novel function that is essential for all cells to produce mRNA. Motor neurons appear to be particularly sensitive to defects in SMN, so much so that a deficiency in SMN leads to the death of these cells and results in the atrophy of the muscles they control.

The group's findings will be published in tomorrow's issue of Cell. A full-page photo of a human cell whose nuclear structures have been drastically affected by a mutant SMN protein is featured on the cover of the journal.

"This paper is an important step towards an effective treatment for spinal muscle atrophy," states Kenneth H. Fischbeck, MD, chief of the Neurogenetics Branch at the National Institute of Neurological Disease and Stroke and a former Penn neurologist. "Now scientists will be able to work back from the biochemistry of the disease to eventually design new therapies."

The findings demonstrate that the SMN protein plays a crucial role in the genesis of mRNA from a precursor called pre-mRNA. The conversion of pre-mRNA to mRNA takes place in the cell nucleus in a process called splicing. It is a critical step in the pathway of gene expression, and ultimately, in the production of a functional protein.

This genetic splicing is analogous to splicing a film together--getting the right sequence, cutting out the unnecessary parts, and putting it back together in the right order. "Obviously, this splicing process needs to operate efficiently and with high fidelity," explains Dreyfuss. "A complex molecular machine assembles on each pre-mRNA to carry out the splicing process. This is a modular splicing machine that is re-used repeatedly, cycle after cycle. It is comprised of many proteins and of small specialized particles called snRNPs. Our research shows that SMN and its entourage of helper proteins are required for the proper form and function of snRNPs and for maintaining the splicing machine in an active form so that it can be used for multiple rounds of splicing."

In cells of patients with spinal muscle atrophy, the splicing process is drastically compromised. Human motor neurons contain some of the highest concentrations of snRNPs, as well as SMN, of any cells in the body. When there is a deficiency of SMN, the motor neurons appear to be the first cells to suffer, and cell death eventually results.

As part of this work, the team has re-created the biochemical activity of SMN in a test tube. "This should make it possible to directly search for compounds that may enhance or substitute for SMN's activity, and thus serve as potential drugs for treating spinal muscle atrophy," adds Dreyfuss.


Story Source:

The above story is based on materials provided by University Of Pennsylvania Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Pennsylvania Medical Center. "Molecular Basis Of Leading Genetic Cause Of Infant Death Discovered." ScienceDaily. ScienceDaily, 26 November 1998. <www.sciencedaily.com/releases/1998/11/981126103525.htm>.
University Of Pennsylvania Medical Center. (1998, November 26). Molecular Basis Of Leading Genetic Cause Of Infant Death Discovered. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/1998/11/981126103525.htm
University Of Pennsylvania Medical Center. "Molecular Basis Of Leading Genetic Cause Of Infant Death Discovered." ScienceDaily. www.sciencedaily.com/releases/1998/11/981126103525.htm (accessed August 1, 2014).

Share This




More Health & Medicine News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Despite Health Questions, E-Cigs Are Beneficial: Study

Despite Health Questions, E-Cigs Are Beneficial: Study

Newsy (July 31, 2014) Citing 81 previous studies, new research out of London suggests the benefits of smoking e-cigarettes instead of regular ones outweighs the risks. Video provided by Newsy
Powered by NewsLook.com
Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
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