Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists discover RNA modifications in some unexpected places

16.09.2014

The so-called central dogma of molecular biology—that DNA makes RNA which makes protein—has long provided a simplified explanation for how genetic information is deciphered and translated in living organisms.

In reality, of course, the process is vastly more complicated than the schema first articulated nearly 60 years ago by Nobel Laureate Francis Crick, co-discoverer of the DNA's double-helix structure.

For one, there are multiple types of RNA, three of which—messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA)—are essential for proper protein production. Moreover, RNAs that are synthesized during the process known as transcription often undergo subsequent changes, which are referred to as "post-transcriptional modifications."

Multiple such RNA modifications have been documented over the years, although the precise functions and significance of many of these have been shrouded in mystery. Among the most common post-transcriptional modifications is pseudouridylation, during which the base nucleoside uridine—the 'U' of the four base RNA nucleosides abbreviated as A, C, T, and U—has its chemical structure altered to form a molecule known as pseudouridine (ψ). To date, ψ has been found in abundance in tRNA, rRNA, and small nuclear or snRNA, but was thought not to exist in mRNA.

Until now.

Deploying sophisticated high-throughput sequencing technology, dubbed ψ-seq, a team of Whitehead Institute and Broad Institute researchers collaborated on a comprehensive, high-resolution mapping of ψ sites that confirms pseudouridylation does indeed occur naturally in mRNA. This somewhat surprising finding and the novel approach that led to it are revealed online this week in the journal Cell.

"This is really a better, more quantitative method to measure this modification, which is interesting in and of itself," says Douglas Bernstein, a co-first author of the Cell paper. "Finding the modification in mRNA was an unexpected bonus."

Bernstein, a postdoctoral researcher in the lab of Whitehead Institute Founding Member Gerald Fink, collaborated with postdoc Schragi Schwartz and Max Mumbach in the lab of Broad Institute Core Member Aviv Regev to orchestrate the ψ mapping in yeast. Having discovered pseudouridylation at dozens of sites in mRNA, the group set out to determine the functional role of the modification.

Knowing that pseudouridylation is catalyzed by enzymes known as pseudouridine synthases (PUS) the group looked for differences in mRNA pseudouridylation between a normal, wild-type yeast strain and a mutant strain with a PUS gene deleted. Intriguingly, heat shock dramatically increased the number of mRNA pseudouridylation sites in the normal strain but not in the mutant strain. Further, the group found that pseudouridylated genes were expressed at roughly 25% higher levels in the wild type strains than in the genetically modified strains.

Taken together, these findings suggest that heat shock activates a dynamic pseudouridylation program in yeast that may lead to beneficial outcomes for the organism, perhaps by increasing mRNA stability under adverse conditions.

While the research begins to outline a role for pseudouridylation of mRNA in yeast, its methodology and findings are likely to have implications in humans as well. As part of this work, the scientists performed ψ-seq on a line of human cells as well, finding remarkable similarity in mRNA pseudouridylation sites between human and yeast cells. Notably, a number of human diseases, including dyskeratosis congenita, which is characterized by a predisposition to cancer and bone marrow failure, are associated with mutations in PUS genes, suggesting that ψ-seq may have applications in uncovering the significance of RNA pseudouridylation in human pathologies.

###

This work is supported by the National Institutes of Health (grants GM035010 and 1F32HD075541-01), the National Human Genome Research Institute (grants P50HG006193 and U54HG003067), the Howard Hughes Medical Institute, Broad Institute Funds, the Marie Curie IOF, and the Swiss National Science Foundation.

Written by Matt Fearer

Gerald Fink's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology at Massachusetts Institute of Technology.

Full Citation:

"Transcriptome-wide Mapping Reveals Widespread Dynamic-Regulated Pseudouridylation of ncRNA and mRNA"
Cell, September 11, 2014 (online)

Schraga Schwartz (1), Douglas A. Bernstein (2), Maxwell R. Mumbach (1), Marko Jovanovic (1), Rebecca H. Herbst (1,3), Brian X. Leo´n-Ricardo (1,4) Jesse M. Engreitz (1), Mitchell Guttman (5) Rahul Satija (1), Eric S.Lander (1,3,6) Gerald Fink (2,6), and Aviv Regev (1,6,7)

1. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
2. Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
3. Department of Systems Biology, Harvard Medical School, Boston, MA 02114, USA
4. Department of Biology, University of Puerto Rico, Rio Piedras Campus, San Juan 00931, Puerto Rico
5. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
6. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
7. Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA

Matt Fearer | Eurek Alert!
Further information:
http://www.mit.edu

Further reports about: Biology Biomedical Medical RNA mRNA modification modifications strain structure

More articles from Life Sciences:

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

nachricht Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>