Until 2001, few people had heard the term micro ribonucleic acids, but these little chunks of nucleic acid, just 21 to 23 bases long, have been conserved throughout evolution. They don’t code for proteins, but they do seem to be involved in the regulation of immunity, the development and differentiation of immune cells, antibody production and the release of chemicals involved in the inflammatory response. So micro by name, but not by nature, you might say.

Indeed, microRNA, or miRNA, represent something of a new paradigm in the regulation of a vast array of responses of physiological and hence medical importance. They play a key role in diverse such diverse areas as virology, embryogenesis, differentiation of stem cells, cholesterol and fat metabolism, inflammation and (of course) cancer.

Victor Ambros, Rosalind Lee and Rhonda Feinbaum, at Harvard University, first revealed the existence of miRNA through studies with the lin-4 gene, an essential component of normal developmental in the lab technician’s favourite nematode Caenorhabditis elegans. They demonstrated that the lin-4 gene sequence from four species of nematode worm does not encode for a protein. That was an odd finding because nucleic acid sequences generally do. Instead it seemed that lin-4 regulates a so-called antisense RNA to RNA interaction. That was way back in 1993.

By 2001, the year the term miRNA was coined, these little chunks of RNA were becoming much more well known as the controls for post-transcriptional regulatory mechanisms. Since then it has been recognised that miRNAs are involved in the development of cardiovascular disease, hepatitis C, Alzheimer’s, and various forms of cancer. Wherever an important molecule emerges in biological research you can bet the notion of targeting that molecule with other molecules, pharmaceuticals, will be the next stage in the research.

Bioinformatics specialists Virendra Gomase and and Akshay Parundekar of the Padmashree Dr. D.Y. Patil University, in Mumbai, India, recently reported that miRNAs having been implicated in a range of diseases are now attractive targets for the development of new drugs. They explain that one approach to silencing miRNAs and so inhibiting the progression of various diseases is through the use of antagomirs.

Antagomirs are small molecules that resemble the oligonucleotides used to build RNA, but they are modified chemically so that they are not simply incorporated into working miRNA but block it by distorting it structurally or chemically. These compounds are, of course, related to the drugs used to treat RNA viruses, such as acyclovir, which is an analogue of the RNA oligonucleotide guanosine.

Studies have already demonstrated that antagomirs administered intravenously against various miRNAs – miR-16, miR-122, miR-192, and miR-194 – result in a marked reduction in levels of each miRNA in liver, lung, kidney, heart, intestine, fat, skin, bone marrow, muscle, ovaries and kidneys. Apparently, this method of silencing miRNAs in the body is specific (meaning fewer side-effects) and long-lasting (which means efficacious). But, the approach is still in its infancy, Gomase and Parundekar point out.

Indeed, they explain that in order to understand the enigma of gene expression as regulated by miRNA, there is a triangle of three parameters that must be unravelled:

  1. Regulation (if any) of a gene at transcriptional level
  2. Regulation of the transcript of that gene by microRNA
  3. Regulation of that microRNA itself

Once that happens…

“The evolution of microRNA-omics will open up the possibility of potent future diagnostics and therapeutics for serious diseases,” the team concludes.

Research Blogging Icon Virendra S. Gomase, & and Akshay N. Parundekar (2009). microRNA: human disease and development Int. J. Bioinformatics Research and Applications, 5 (5), 479-500