Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New roles emerge for non-coding RNAs in directing embryonic development

29.08.2011
Global view of 'lincRNAs' reveals critical role in regulation of embryonic stem cells

Scientists at the Broad Institute of MIT and Harvard have discovered that a mysterious class of large RNAs plays a central role in embryonic development, contrary to the dogma that proteins alone are the master regulators of this process. The research, published online August 28 in the journal Nature, reveals that these RNAs orchestrate the fate of embryonic stem (ES) cells by keeping them in their fledgling state or directing them along the path to cell specialization.

Broad scientists discovered several years ago that the human and mouse genomes encode thousands of unusual RNAs — termed large, intergenic non-coding RNAs (lincRNAs) —but their role was almost entirely unknown. By studying more than 100 lincRNAs in ES cells, the researchers now show that these RNAs help regulate development by physically interacting with proteins to coordinate gene expression and suggest that lincRNAs may play similar roles in most cells.

"There's been a lot of debate about what lincRNAs are doing," said Eric Lander, director of the Broad Institute and the senior author of the paper. "It's now clear that they play critical roles in regulating developmental decisions — that is, cell fate. This was a big surprise, because specific types of proteins have been thought to be the master controls of development."

"This is the first global study of lincRNAs," said Mitchell Guttman, first author of the paper and a graduate student at MIT and the Broad Institute. "We picked embryonic stem cells in particular because they are so important to development and so well understood. This allowed us to dissect the role of lincRNAs within the circuitry of a cell."

The researchers used genetic tools to inhibit more than 100 lincRNAs and found that the vast majority — more than 90 percent — had a significant impact on embryonic stem cells, indicating that the RNAs play a key role in the cells' circuitry.

Embryonic stem cells can follow one of two main routes. They can either differentiate, becoming cells of a specific lineage such as blood cells or neurons, or they can stay in a pluripotent state, duplicating themselves without losing the ability to become any cell in the body. When the researchers turned off each lincRNA in turn, they found dozens that suppress genes that are important only in specific kinds of cells. They also found dozens of lincRNAs that cause the stem cells to exit the pluripotent state.

"It's a balancing act," said Guttman. "To maintain the pluripotent state, you need to repress differentiation genes."

The researchers also uncovered a critical clue about how lincRNAs carry out their important job. Through biochemical analysis, they found that lincRNAs physically interact with key proteins involved in influencing cell fate to coordinate their responses.

"The lincRNAs appear to play an organizing role, acting as a scaffold to assemble a diverse group of proteins into functional units," said John Rinn, an author on the paper, an assistant professor at Harvard University and Medical School, and a senior associate member of the Broad Institute. "lincRNAs are like team captains, bringing together the right players to get a job done."

"By understanding how these interactions form, we may be able to engineer these RNAs to do what we want them to do," said Guttman. "This could make it possible to target key genes that are improperly regulated in disease."

Aviv Regev, an author on the paper, a core member of the Broad Institute, and associate professor at MIT, sees the team's approach to studying the lincRNAs as important for the field. "Many people are interested in lincRNAs, but they need a comprehensive view of the whole collection of lincRNAs," said Regev. "The large-scale data and technology from this study will be useful for scientists worldwide in studying both lincRNAs as well as many other RNAs in the cell."

This project marks a collaborative effort involving experts in embryonic stem cells and lincRNAs as well as computational biologists and researchers in the Broad's RNAi Platform, which developed the tools needed to systematically silence lincRNAs. Other researchers who contributed to this work include Julie Donaghey, Bryce W. Carey, Manuel Garber, Jennifer K. Grenier, Glen Munson, Geneva Young, Anne Bergstrom Lucas, Robert Ach, Xiaoping Yang, Ido Amit, Alexander Meissner, and David E. Root. This work was funded by the National Human Genome Research Institute, the Richard Merkin Foundation for Stem Cell Research at the Broad Institute, and funds from the Broad Institute of MIT and Harvard.

-Written by Haley Bridger, Broad Institute

Paper cited:

Guttman M et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature. August 28, 2011 DOI: 10.1038/nature10398

About the Broad Institute of Harvard and MIT

The Eli and Edythe L. Broad Institute of Harvard and MIT was launched in 2004 to empower this generation of creative scientists to transform medicine. The Broad Institute seeks to describe all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods and data openly to the entire scientific community.

Founded by MIT, Harvard and its affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide. For further information about the Broad Institute, go to http://www.broadinstitute.org.

About the Richard Merkin Foundation for Stem Cell Research at the Broad Institute

The Richard Merkin Foundation for Stem Cell Research at the Broad Institute seeks to fund Broad Institute-affiliated scientists to develop a novel and comprehensive "toolbox" of experimental methods and computational algorithms and to apply those tools to understand cellular circuitry in stem cells, with the goal of being able to manipulate those circuits for both biological knowledge and medical applications.

For more information, contact:

Broad Institute of MIT and Harvard
Haley Bridger
617.714.7968
hbridger@broadinstitute.org

Haley Bridger | EurekAlert!
Further information:
http://www.broadinstitute.org

More articles from Life Sciences:

nachricht Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society

nachricht 127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

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

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>