Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New resource to unlock the role of microRNAs

08.08.2011
Comprehensive set of mutated mouse microRNAs will drive research

A new resource to define the roles of microRNAs is announced today in Nature Biotechnology. The resource, called mirKO, gives researchers access to tools to investigate the biological role and significance for human health of these enigmatic genes.

mirKO is a "library" of mutant mouse embryonic stem (ES) cells in which individual, or clustered groups of microRNA genes, have been deleted. Using these tools researchers can create cells or mice lacking specific microRNAs, study expression using fluorescent markers, or inactivate the gene in specific tissues or at specific times in development. This is the first mammalian microRNA knockout resource; the only other comprehensive resource of mutated microRNA genes is that for the nematode worm.

microRNAs – first named only ten years ago – are encoded by more than 500 genes that are predicted to regulate about one third of protein-coding genes. Consisting of short stretches of 21 to 23 nucleotides, microRNAs act by interfering with the activity of messenger RNAs. Studies over the past five years have shown that microRNAs are likely to play important roles in disease such as cancer and disorders of the heart, the immune system and auditory systems.

"We have generated a resource of microRNA knockout alleles in mouse ES cells that are standardized with respect to design and genetic background that researchers can access through repositories," says Dr Haydn Prosser, lead author on the research from the Wellcome Trust Sanger Institute. "In many cases, microRNAs with overlapping messenger RNA target specificities occur at multiple locations throughout the genome. To address these complexities a comprehensive resource is valuable to enable the creation of compound mutants in cells or mice."

The first step was to develop DNA vectors to target the microRNA genes: the team produced two alternative vectors that could, if desired, be used to knock out both copies of a particular microRNA in mouse ES cells.

The team inserted newly designed DNA vectors in place of the microRNA genes, successfully knocking out about 400 so far.

"The biology of microRNAs will be revealed only when we can rigorously examine their activity, their role in individual tissues, and at specific times in development," says Professor Allan Bradley, senior author on the study and Director Emeritus of the Sanger Institute. "Our paper shows that the tools within mirKO can do that.

"We have tagged genes with a colour reporter, developed a mutation that can be induced when required and produced mice carrying mutations. This is an important proof of principle."

In previous research, Professor Bradley's team showed that a specific microRNA played a role in the development of a component of the immune system: in its absence, mice develop signs similar to those of human autoimmune disease and are less resistant to infection.

The resource is built on cassettes of genetic components that can be swapped through a technology called recombinase mediated cassette exchange (RMCE). "We have designed the targeted alleles to be adaptable in order that researchers can efficiently alter particular microRNA loci in a multitude of alternative ways to provide information additional to straightforward null mutants. In this respect we have developed a research toolbox that will help researchers define the role of microRNAs in health and disease,"says Haydn Prosser.

In one configuration the wildtype microRNA locus was reconstituted while being flanked by recombinase sites in order to facilitate time- or tissue-specific expression. A second RMCE cassette contains a gene that produces a red fluorescent protein: when this is swapped into a mutated microRNA gene, it reflects the activity of the mouse microRNA gene so its activity can be studied. The team showed that this method accurately reflected the known activity of two microRNA loci.

The developing suite of tools has already been invaluable to researchers. "This is clearly a valuable resource which will make research easier and more efficient," says Eric Miska, a group leader at the Wellcome Trust/Cancer Research UK Gurdon Institute in Cambridge."In our research into regulatory RNAs, we are using this resource to investigate the role of individual microRNAs during early development and how their deregulation might contribute to the etiology of cancer."

Information and details of the mirKO resource can be accessed through the International Mouse Knockout Consortium (http://www.knockoutmouse.org/martsearch). The biological materials are being transferred to repositories for distribution to the research community.

Notes to Editors

Publication Details
Prosser HM et al (2011). A resource of vectors and ES cells for targeted deletion of microRNAs in mice. Nature Biotechnology, published online on Sunday, 7 August 2011

doi: 10.1038/nbt.1929.

Funding

This work was funded by the Wellcome Trust.

The International Knockout Mouse Consortium database was developed with funding from the European Union and the US National Institutes of Health.

The Wellcome Trust/Cancer Research UK Gurdon Institute

The Wellcome Trust/Cancer Research UK Gurdon Institute is part of Cambridge University. Funding from its two main sponsors, and other sources, supports research into the complementary areas of Cancer and Developmental Biology. http://www.gurdon.cam.ac.uk/about.html

The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to exploit the wealth of genome data now available to answer important questions about health and disease. http://www.sanger.ac.uk

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.

Don Powell | EurekAlert!
Further information:
http://www.sanger.ac.uk
http://www.wellcome.ac.uk

More articles from Life Sciences:

nachricht Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)

nachricht CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

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...

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

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>