Featured Research

from universities, journals, and other organizations

New Components Of Machinery That Carries Genetic Information From Nucleus

Date:
July 6, 1999
Source:
Duke University
Summary:
Researchers have reported discovering the first elements of what is apparently a molecular signaling pathway important for regulating how genetic information leaves the nucleus to begin its working life as a blueprint for the cell.

DURHAM, N.C. -- Researchers have reported discovering the first elements of what is apparently a molecular signaling pathway important for regulating how genetic information leaves the nucleus to begin its working life as a blueprint for the cell.

According to the scientists, their finding represents an intriguing new role for a signaling molecule, derived from inositol, in the cell.

In an article in the July 2 Science, Duke University Medical Center pharmacologist John York and his colleagues reported studies in yeast that revealed the presence of enzymes called kinases ? enzymes that add phosphates to inositol to make them into signals that trigger the export of messenger RNA from the cell nucleus.

Messenger RNA (mRNA) is the molecule that, when copied from DNA genes in the nucleus, carries genetic information into the cell where it is used to build proteins.

Co-authors on the article are Audrey Odom, also of Duke, and Robert Murphy, Eric Ives and Susan Wente of Washington University School of Medicine. York is an assistant professor of pharmacology and cancer biology, and of biochemistry. Odom is a graduate student in the Medical Scientist Training Program. The research was sponsored by the Burroughs Wellcome Fund, the National Institutes of Health and the American Cancer Society.

While York emphasizes that the discovery is very basic in nature, and was made using yeast, such fundamental knowledge invariably contributes to understanding and treatment of human disease, he said. Particularly important, he emphasized, is that inositol signaling is critical to the machinery of living cells, and many of its components are conserved all the way from yeast to humans.

Inositols had already been suspected of being major signaling molecules in the cell, because some 20 different inositols had been discovered with varying numbers and arrangements of phosphates attached, like a multitude of keys with slightly different shapes. However, researchers still do not understand where and when the cell uses these molecular keys, and which locks they open.

The most well-known inositol, IP3, has three phosphates attached, and is produced in the cell in response to stimuli, via the action of a key enzyme called phospholipase C. IP3 is known to be critical for triggering the release of calcium, which in turn triggers other cell processes.

However, York and his colleagues to their surprise had found that IP3 apparently has yet unknown extended signaling roles, produced when additional phosphates are added to produce IP4, IP5 and IP6 in the cell. Production of these IPs also depends on phospholipase C activity in cells.

The latest research began when York contacted Wente, after learning through colleague Jeremy Thorner of the University of California-Berkeley that Wente had discovered a link between a phospholipase C and an essential factor GLe-1 that is essential for transporting mRNA out of the nucleus. Of particular interest was that Wente had also discovered that two other genes of unknown function also linked to GLe-1.

York theorized that the other two genes might be the blueprints for two new kinases responsible for adding phosphates to IP3 on the way to producing IP6.

"It was easy to test this hypothesis," said York. "We just introduced radio-labeled inositol into yeast strains mutated to lack the genes for one or the other of the suspected kinases. Depending on the kinase blocked, we expected to see buildup of either IP3 or IP5, with no IP6 in any case." Sure enough, said York, the experiments indicated that the mysterious genes coded for kinases, or at least their regulators, transformed IP3 to IP4, and IP5 to IP6.

According to York, still to be determined is whether IP6 directly or indirectly affects the transport of mRNA from the nucleus. IP6 may merely regulate the "gatekeeper" -- called the Nuclear Pore Complex -- a huge protein machine that controls the passage of mRNA and other substances out of the nucleus. Or, IP6 may directly affect the protein "package" that carries mRNA through the Nuclear Pore Complex.

Especially intriguing, said York, is that inositol signals are not absolutely necessary for mRNA to leave the nucleus, except at high temperatures.

"One idea is that this process is involved only in transport of specific genes that are needed to help cells adapt to stress, such as heating," he said.

Future studies will aim at identifying the protein that is the target of the IP6 signal and how it affects that protein to act as a switch. More broadly, the discovery of the two kinases has helped open up an important new research pathway, emphasized York.

"This discovery really challenges the idea that IP3 was the sole signal coming from this pathway," he said. "In fact, we know now it's not. Now we know that while this pathway begins by affecting calcium, it ends with the export of mRNA from the nucleus as mediated by IP6. We now want to find out what are the signaling roles of each molecules along this pathway, and in fact whether there's a signal after IP6."

Even broader, said York, the research offers even more hints that inositols have extremely complex signaling roles, including specialized roles in different compartments of the cell and at different times.


Story Source:

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


Cite This Page:

Duke University. "New Components Of Machinery That Carries Genetic Information From Nucleus." ScienceDaily. ScienceDaily, 6 July 1999. <www.sciencedaily.com/releases/1999/07/990706070513.htm>.
Duke University. (1999, July 6). New Components Of Machinery That Carries Genetic Information From Nucleus. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/1999/07/990706070513.htm
Duke University. "New Components Of Machinery That Carries Genetic Information From Nucleus." ScienceDaily. www.sciencedaily.com/releases/1999/07/990706070513.htm (accessed July 29, 2014).

Share This




More Plants & Animals News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (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
Asteroid's Timing Was 'Colossal Bad Luck' For The Dinosaurs

Asteroid's Timing Was 'Colossal Bad Luck' For The Dinosaurs

Newsy (July 28, 2014) The asteroid that killed the dinosaurs struck at the worst time for them. A new study says that if it hit earlier or later, they might've survived. Video provided by Newsy
Powered by NewsLook.com
Raw: Sea Turtle Hatchlings Emerge from Nest

Raw: Sea Turtle Hatchlings Emerge from Nest

AP (July 27, 2014) A live-streaming webcam catches loggerhead sea turtle hatchlings emerging from a nest in the Florida Keys. (July 27) Video provided by AP
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