Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The Fragile X syndrome protein as RNA distribution hub

06.02.2003


New technique tracks RNAs associated with the protein responsible for Fragile X



The process of turning genes into protein makes the insides of cells terribly crowded and complicated places. Signals tell machinery to transcribe the DNA of genes into messenger RNA (mRNA) whose translation into protein has to be coordinated with everything else that is happening within the cell. Fortunately, there are RNA binding proteins to organize mRNAs. These proteins are so critical that the loss of one particular RNA binding protein, FMRP, leads to Fragile X syndrome, the most common inherited forms of mental retardation.

Researchers based at the University of Pennsylvania School of Medicine invented a technique called Antibody Positioned RNA Amplification (APRA) to determine the identity of RNA molecules associated with RNA binding proteins. Their findings on FMRP, presented in the February 6th issue of the journal Neuron, further define the complex basis of Fragile X syndrome.


Fragile X syndrome is the most common inherited cause of mental retardation in both men and women. The disorder causes mental abnormalities that range from slight learning disabilities to severe mental retardation. The syndrome is caused by a mutation in what has been termed the Fragile X mental retardation-1 (Fmr1) gene, which encodes FMRP, the Fragile X mental retardation protein.

"RNA-binding proteins regulate all aspects of RNA synthesis, such as mRNA transcription, splicing and editing, as well as translation of mRNA into protein," said James Eberwine, PhD, professor in Penn’s Department of Pharmacology. "The mRNAs held by FMRP encode for proteins that assist in transmitting signals within the brain. FMRP provides cellular mRNA traffic control, and moves selected mRNAs to sites where they can be translated. How FMRP knows where to move these mRNAs and how these mRNAs are released from FMRP is unclear at present."

To study how RNA binding proteins such as FMRP function, Eberwine and his colleagues developed a technique to identify specific mRNAs associated with a particular binding protein. At its basis, APRA enables researchers to analyze an RNA binding protein’s cargo on a genome-wide basis.

In practice, APRA works a bit like a homing beacon attached to a photocopier: Eberwine connected an antibody that specifically binds to FMRP to a DNA molecule that can bind to the RNA near the FMRP protein. In the presence of enzymes, the DNA molecule helps copy these RNAs into cDNA (a term for DNA made from RNA).

After it is synthesized, the cDNA is amplified into hundreds of thousands of RNA molecules by an amplification procedure also developed in the Eberwine lab a few years ago. These amplified RNA molecules can be screened against a microarray to identify their corresponding genes. In this bridging of genomics (the study of the genome) and proteomics (global analysis of proteins), the specificity of the antibody’s attraction to FMRP induces the specificity of the RNA analysis. Given the nature of Fragile X syndrome – and the fact that FMRP is found only in the tissues of the central nervous system – the researchers were encouraged to find that among the FMRP’s cargo are mRNAs encoding proteins involved in transmitting signals between neurons and in neuron maturation.

As a research tool, the researchers believe that APRA analysis has great potential for researchers who want to target specific RNA binding proteins for analysis. Given its specificity, ARPA can track down RNA binding proteins that are only found in certain tissues and examine those proteins under varying physiological conditions or disease states.

"In that sense, APRA could mean to RNA studies as much as DNA and RNA amplification techniques have meant to studying the genome," said Eberwine. "It is also part of the growing frontier of molecular biology – somewhere between genomics and proteomics is the interplay of RNA with RNA-binding proteins."

Researchers also involved in these findings include: lead author Kevin Miyashiro of Penn’s Department of Pharmacology; Andrea Beckel-Mitchener, T. Patrick Purk, Ivan Jeanne Wieler, Willam T. Greenough, of the Beckman Institute at the University of Illinois; Lei Liu of the W.M. Keck Center for Comparative and Functional Genomics at the University of Illinois; Salvatore Carbonetto of the Centre for Neuroscience Research at McGill University; and Kevin G. Becker and Tanya Barret of the DNA Array Unit of the National Institute on Aging.


###
This research was funded through grants from the National Institute on Aging and the National Institute of Mental Health.

Greg Lester | EurekAlert!
Further information:
http://www.med.upenn.edu/

More articles from Life Sciences:

nachricht New technique to determine protein structures may solve biomedical puzzles
11.12.2019 | Dana-Farber Cancer Institute

nachricht NTU Singapore scientists convert plastics into useful chemicals using su
11.12.2019 | Nanyang Technological University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Highly charged ion paves the way towards new physics

In a joint experimental and theoretical work performed at the Heidelberg Max Planck Institute for Nuclear Physics, an international team of physicists detected for the first time an orbital crossing in the highly charged ion Pr⁹⁺. Optical spectra were recorded employing an electron beam ion trap and analysed with the aid of atomic structure calculations. A proposed nHz-wide transition has been identified and its energy was determined with high precision. Theory predicts a very high sensitivity to new physics and extremely low susceptibility to external perturbations for this “clock line” making it a unique candidate for proposed precision studies.

Laser spectroscopy of neutral atoms and singly charged ions has reached astonishing precision by merit of a chain of technological advances during the past...

Im Focus: Ultrafast stimulated emission microscopy of single nanocrystals in Science

The ability to investigate the dynamics of single particle at the nano-scale and femtosecond level remained an unfathomed dream for years. It was not until the dawn of the 21st century that nanotechnology and femtoscience gradually merged together and the first ultrafast microscopy of individual quantum dots (QDs) and molecules was accomplished.

Ultrafast microscopy studies entirely rely on detecting nanoparticles or single molecules with luminescence techniques, which require efficient emitters to...

Im Focus: How to induce magnetism in graphene

Graphene, a two-dimensional structure made of carbon, is a material with excellent mechanical, electronic and optical properties. However, it did not seem suitable for magnetic applications. Together with international partners, Empa researchers have now succeeded in synthesizing a unique nanographene predicted in the 1970s, which conclusively demonstrates that carbon in very specific forms has magnetic properties that could permit future spintronic applications. The results have just been published in the renowned journal Nature Nanotechnology.

Depending on the shape and orientation of their edges, graphene nanostructures (also known as nanographenes) can have very different properties – for example,...

Im Focus: Electronic map reveals 'rules of the road' in superconductor

Band structure map exposes iron selenide's enigmatic electronic signature

Using a clever technique that causes unruly crystals of iron selenide to snap into alignment, Rice University physicists have drawn a detailed map that reveals...

Im Focus: Developing a digital twin

University of Texas and MIT researchers create virtual UAVs that can predict vehicle health, enable autonomous decision-making

In the not too distant future, we can expect to see our skies filled with unmanned aerial vehicles (UAVs) delivering packages, maybe even people, from location...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The Future of Work

03.12.2019 | Event News

First International Conference on Agrophotovoltaics in August 2020

15.11.2019 | Event News

Laser Symposium on Electromobility in Aachen: trends for the mobility revolution

15.11.2019 | Event News

 
Latest News

Self-driving microrobots

11.12.2019 | Materials Sciences

Innovation boost for “learning factory”: European research project “SemI40” generates path-breaking findings

11.12.2019 | Information Technology

Molecular milk mayonnaise: How mouthfeel and microscopic properties are related in mayonnaise

11.12.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>