Lorne 2012: Modelling microRNAs

Lorne Genome: The humble fruit fly is teaching us how microRNAs seem to be punching above their weight in an ever-growing list of biological functions in health and disease.

Fiona Wylie (Australian Life Scientist)
15 February, 2012 10:45
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MicroRNAs (miRNAs) work by modifying gene expression at the post-translational level across a range of species, from plants to worms to humans.

Discovered only in 1993, it is now clear that miRNAs, while not coding for proteins, have a tremendous impact on the gamut of mammalian functions, including cell growth and proliferation, development, apoptosis, immune function and metabolism.

These tiny stretches of ribonucleic acid (only 21-23 bases) bind to complementary sequences on target messenger RNA transcripts to usually shelve the transcriptional information (gene silencing) and thus effectively act as negative regulators of gene expression.

As may be expected, aberrant expression of miRNA has also been named and shamed in a range of disease processes, fueling a whole new field of research aimed at finding miRNA-based targets for diagnostics and therapies.

One of the most respected names in the field of Drosophila genetics is Dr Stephen Cohen from the Institute of Molecular and Cell Biology (IMCB) in Singapore, who in February will head to the sunny but cooler climes of Lorne for the 2012 Lorne Genome conference.

Cohen’s lab uses the fruit fly as a genetic model for the study of cancer, metabolic disease and neurodegeneration and in recent years has focussed on understanding the biological functions of miRNAs in this context.

All animal genomes have miRNA genes, explains Cohen. In fact, up to five per cent of all genes are thought to be miRNAs.

“Latest estimates put the regulatory capacity of miRNAs at 100s of potential targets for each individual miRNA, so they are similar to transcription factors in that respect. miRNAs could potentially regulate 50 per cent or more of the protein-coding genes in animal genomes based on the predicted miRNA target sites in those genes.

“Over several years we and others have found that miRNAs are key regulators of a range of biological processes relevant to development and disease, including cell growth, death and metabolism,” says Cohen.

“In disease, the miRNA is sometimes misexpressed, leading to inappropriate downregulation of genes that might be important for normal function. Other times, miRNA expression is lost and, because of that absence, the levels of some genes go up and that may be detrimental.”

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