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 Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>