Featured Research

from universities, journals, and other organizations

New mechanism in the regulation of human genes

Date:
July 22, 2011
Source:
Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health
Summary:
In order to create proteins, a protein-coding gene must be transcribed into RNA and in the splicing process shortened to the correct template. Scientists in Germany have now discovered how the U2AF protein enables this process.

Top: The central dogma of molecular biology: DNA is transcribed into RNA, from which protein is then formed. Splicing – the removal of the introns from the mRNA – is an essential step in the process. Dysregulated splicing can cause many diseases, including cancer. Bottom: Binding of the splicing factor U2AF to the RNA with and without conformational changes. Both conformations are in equilibrium.
Credit: Image courtesy of Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health

In order to create proteins, the protein-coding gene must be transcribed into RNA and in the so-called splicing process shortened to the correct template. Scientists at the Helmholtz Zentrum München and Munich's Technical University have now discovered how the U2AF protein enables this process.

Related Articles


The results have been published in the current edition of the journal Nature.

Scientists at the Helmholtz Zentrum München and the Technical University of Munich (TUM) along with their colleagues from the European Molecular Biology Laboratory (EMBL) in Heidelberg and the Centre for Genomic Regulation in Barcelona have discovered how the U2AF protein enables the pre-mRNA to be spliced to form the mRNA, which serves as a template for protein synthesis in the body.

Splicing requires the cooperation of different proteins, i.e. splicing factors. One such splicing factor, U2AF, was examined by the Munich scientists. It consists of two structural modules and binds to the RNA near the intron-exon boundary.

Professor Michael Sattler, Director of the Institute for Structural Biology at the Helmholtz Zentrum München and Professor of Biomolecular NMR Spectroscopy at the Technische Universität München, summarizes how the U2AF protein contributes towards splicing: "The spatial structure of the U2AF protein alternates between a closed and an open conformation. A matching RNA sequence in the intron causes the U2AF to assume an open conformation, which activates splicing and eventually leads to the removal of the intron."

The intron's RNA sequence determines how effectively this conformational change can be triggered. This shift of balance between the closed and the open form of the U2AF protein occurs through a process of conformational selection, i.e. the RNA binds to a small fraction of the open conformation that already exists even in the absence of RNA. The scientists presume that similar mechanisms -- balanced between a closed, inactive and an open, active conformation -- play an important role in the regulation of many other signal pathways in the cell.

Background

The genes in the human genome have a specific structure. Sections with relevant exons alternate with regions known as introns, which contain irrelevant information that does not encode the corresponding protein. In order for a protein to be produced, pre-messenger RNA (pre-mRNA) first has to be transcribed from the DNA. The pre-mRNA copy is then spliced and the introns are removed, leaving the mRNA; which consists solely of exons. Splicing requires that the introns recognized and accurately excised. Splicing is thus an essential process in the central dogma of molecular biology: genetic information flows in one direction: from the DNA to RNA to proteins.

Genome / gene / DNA / mRNA: Genes are the basis for the synthesis of proteins. In the first step, desoxyribonucleic acid (DNA) is transcribed to form a messenger ribonucleic acid (messenger RNA or mRNA), which in turn provides a template for protein synthesis. An organism's complete set of DNA is known as a genome.

Splicing / exons / introns / (pre-) mRNA: Exons are the DNA sections that encode the amino acid sequence of a given protein. The introns, which lie between the exons, are removed in the splicing process. The pre-mRNA thus is processed to a more mature mRNA.


Story Source:

The above story is based on materials provided by Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. Note: Materials may be edited for content and length.


Journal Reference:

  1. Cameron D. Mackereth, Tobias Madl, Sophie Bonnal, Bernd Simon, Katia Zanier, Alexander Gasch, Vladimir Rybin, Juan Valcárcel, Michael Sattler. Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF. Nature, 2011; DOI: 10.1038/nature10171

Cite This Page:

Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. "New mechanism in the regulation of human genes." ScienceDaily. ScienceDaily, 22 July 2011. <www.sciencedaily.com/releases/2011/07/110714072410.htm>.
Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. (2011, July 22). New mechanism in the regulation of human genes. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2011/07/110714072410.htm
Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. "New mechanism in the regulation of human genes." ScienceDaily. www.sciencedaily.com/releases/2011/07/110714072410.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) — The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) — Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
Powered by NewsLook.com
WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) — Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) — Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. 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