Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mysterious molecules begin to yield their secrets

02.09.2005


Scientists at Scripps Research and GNF demonstrate power of new generalized screen to find function of noncoding RNAs

A team of investigators at The Scripps Research Institute and the Genomics Institute of the Novartis Research Foundation (GNF) have discovered a way to screen hundreds and potentially thousands of "noncoding" RNA molecules to discover their functions within cells.

Unlike traditional RNA, which is copied from DNA to code for a protein, these noncoding RNA molecules are never translated into proteins. But noncoding does not mean uninteresting. There are tens of thousands of noncoding RNA molecules inside human cells, and even if only one percent is functional, that’s still hundreds of molecules that may be participating in the control of cellular functions.



In this week’s issue of the journal Science, the Scripps Research and GNF team reports on an experimental strategy for searching for these undiscovered functions. As a proof of principal, the scientists screened a library of noncoding RNAs, selected one that seemed to play a cellular role, and performed further experiments to prove that it does.

"We have only just hit the tip of the iceberg," says Professor Peter G. Schultz, Ph.D., who holds the Scripps Family Chair and is a professor in the department of Chemistry and The Skaggs Institute of Chemical Biology at Scripps Research. "There’s a whole world of this noncoding RNA."

A Stranger in the Protein Encoding Land

Noncoding RNA has long been regarded as something of a stranger in the protein encoding land of RNA. It falls outside the purview of traditional molecular biologists, who once adhered to a concept called the "central dogma," which held that DNA genes are transcribed into RNA transcripts that are then translated into proteins.

The fact that there is non-coding RNA within cells has been known for several years, but it has only been recently that scientists have begun to appreciate noncoding RNA. Many reports have appeared in the scientific literature describing this RNA that does not encode proteins.

One of the reasons for the turnaround is that scientists have begun to recognize just how abundant noncoding RNA is. In fact, two reports in the same issue of Science this week describe the work of an international consortium of scientists that includes Scripps Florida Professor Claes Wahlestedt showing that there are far more noncoding RNAs than most scientists would have imagined even a few months ago.

The consortium sequenced some 43,553 RNA transcripts isolated from a variety of mammalian cells and tissue. Surprisingly more than half of these RNA transcripts are noncoding. One of the stunning conclusions of these reports is that the amount of noncoding RNA that is being expressed in cells is vast. Wahlestedt and his consortium colleagues found tens of thousands of noncoding RNAs in mammalian cells--a number even larger than the number of protein-encoding genes being expressed. For details on these results, see the Scripps Florida news release at http://www.scripps.edu/news/press/090105b.html.

So if our DNA is expressing a large number of genes and an even larger number of RNA transcripts that do not code for genes, the question is: why would the cell expend so much energy making RNA if that RNA doesn’t do anything? Perhaps some noncoding RNAs play cellular roles. If so, then, what are the noncoding RNAs doing in the cell?

"That’s the million-dollar question," says Neurobiology Professor John Hogenesch, who is the Director of Genome Technologies at Scripps Florida. "Until now we have not had a generalized way of answering it."

Scientists have speculated as to what these noncoding RNAs are doing based on computational approaches and analyses of the sequences, but nobody has come up with a way of experimentally determining whether the noncoding RNAs have a cellular function.

Proof of a Cellular Function

To apply a high-throughput approach to the problem of detecting the function of certain noncoding RNAs, the Scripps Research and GNF teams began by collecting a library of 512 evolutionarily conserved putative noncoding RNAs. Then, the scientists established screens using a technique called RNA interference to "knock down"--or silence--the noncoding RNA within cells.

The cell-based screens were designed then to look for changes, such as the increase or decrease of activity related to a certain cellular protein. In theory, if this change occurs as a sole result of altering the level of a noncoding RNA, then that noncoding RNA stands a good chance of being involved.

Out of the 512 target noncoding RNAs, the screens returned eight "hits"--eight noncoding RNAs that appeared to have function. Six appeared to affect cell proliferation, one influenced the hedgehog (Hh) signal transduction pathway, and the final one was a strong modifier of nuclear factor of activated T-cells (NFAT) signaling. The team decided to examine in detail this last noncoding RNA. Suspecting that it might interact with proteins, they used a technique to trap the proteins with which the noncoding RNA was interacting. There were ten, a few of which were of the class known as "importins," involved in the transport of materials from the cytoplasm to the cell nucleus.

Among these was the protein "nuclear factor of activated T cells" (NFAT). The scientists found that when they blocked the noncoding RNA, the activity of NFAT increased dramatically. For this reason, they dubbed the noncoding RNA the noncoding repressor of NFAT "NRON."

Demonstrating the function of one noncoding RNA like NRON is only the beginning, says Scripps Research Associate Aaron Willingham, Ph.D., who was the first author on the paper. "You could apply this methodology to look for functions of many other noncoding RNAs."

Jason Bardi | EurekAlert!
Further information:
http://www.scripps.edu
http://www.sciencemag.org

More articles from Life Sciences:

nachricht Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>