Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genome-wide Map Shows Precisely Where microRNAs Work

19.06.2009
By using a technique that molecularly cements proteins to RNAs, Rockefeller scientists have decoded a map of microRNA-messenger RNA interactions in the mouse brain, an advance that holds promise for biology and human disease.

MicroRNAs are the newest kid on the genetic block. By regulating the unzipping of genetic information, these tiny molecules have set the scientific world alight with such wide-ranging applications as onions that can’t make you cry and potential new therapeutic treatments for viral infections, cancer and degenerative diseases. But the question remains: How do they work?

In research to appear in the June 17 advance online issue of Nature, Robert B. Darnell, head of the Laboratory of Molecular Neuro-oncology, and his team at Rockefeller University provide a long-awaited key clue to answering that question. By using a technique that molecularly cements proteins to RNAs, the team has decoded a map of microRNA-messenger RNA interactions in the brain, an advance that holds promise for biology and human disease, for example by silencing trouble-making genes linked to disease.

MicroRNAs rewrote the rules of gene expression in 2001 when they were found to bind to messenger RNA and shut down protein production, called RNA interference. By 2006, when the Nobel Prize in medicine was given for the discovery of RNA interference, scientists around the globe had even narrowed down microRNAs’ primary site of action to somewhere around the end of the RNA transcript. What scientists couldn’t nail down was the exact string of nucleotides to which the microRNAs bound along a messenger RNA transcript.

“To understand exactly how microRNAs work, you want to know their precise targets,” says Darnell, who is a Howard Hughes Medical Institute Investigator and Robert and Harriet Heilbrunn Professor at Rockefeller. “You want a map that tells you which messenger RNAs each microRNA targets and exactly where they are binding.”

The problem was that on any given messenger RNA, there are many sites to which a single microRNA can theoretically bind, and there are hundreds of microRNAs in every cell. Prior techniques -- primarily relying on computer predictions -- weren’t very good at sorting through the morass of predictions to identify the real sites, explains Darnell. The trick to getting such a map was to freeze a snapshot of microRNAs directly bound to messenger RNA in living cells. Working specifically in mouse brain tissue, that’s what Darnell and his team did using a technique the lab developed called high throughput sequence-crosslinking immunoprecipitation, or HITS-CLIP.

In order to shut down a gene before it is translated, microRNAs must be guided to their target messenger RNAs via a protein called Argonaute. The Argonaute-microRNA-messenger RNA complex now forms a sandwich structure where the microRNA is compressed in the middle. By using their technique to fuse Argonaute to these two RNAs, the team was then able to identify the bound microRNA and its precise target sites across all messenger RNAs expressed in the mouse brain.

The researchers, including first author Sung-Wook Chi, a graduate fellow in Tri-Institutional Computational Biology Program, Julie Zang, a biomedical fellow, and Aldo Mele, a research assistant, found that on average, about two microRNAs bind to each messenger RNA. They also found that microRNAs do not only bind to nucleotides at the terminal end of a messenger RNA, but also at other regions including sequences coding for proteins, and sequences once thought to be “junk RNA,” providing new insights into microRNA biology.

“It is thought that RNA is the molecule that can explain the gap between the complexity of cellular functions and our limited number of genes,” says Darnell. “We now have a platform to evaluate the degree to which microRNAs contribute to this complexity with an extraordinary amount of precision.”

This research was supported in part by the U.S. National Institutes of Health.

Thania Benios | Newswise Science News
Further information:
http://www.rockefeller.edu

More articles from Life Sciences:

nachricht Embryonic development: How do limbs develop from cells?
18.05.2018 | Humboldt-Universität zu Berlin

nachricht Reading histone modifications, an oncoprotein is modified in return
18.05.2018 | American Society for Biochemistry and Molecular Biology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>