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
|Contact: Don Powell|
Wellcome Trust Sanger Institute