By Dr Tomislav Meštrović, MD, PhD
Gene expression in cells and tissues of every complex organism is precisely controlled and largely dependent on different conditions (such as development, changes in the environment, diseases or drugs). Various cells and organ systems within such organism (including humans) contain different gene expression profiles, thus proper understanding of regulatory mechanisms involved in such expression represents one of the key issues in genomic medicine.
Non-coding RNA molecules have a role in plethora of regulatory events – from controlling the number of copies in bacterial division to X-chromosome inactivation in mammals. Recent analyses of the human and animal genomes have shown that most of RNA transcripts do not code for proteins (i.e. they are messenger RNAs or mRNAs), but are instead noncoding RNAs (ncRNAs).
MicroRNAs (or miRNAs) comprise a novel class of small, non-coding endogenous RNAs that regulate gene expression by directing their target mRNAs for degradation or translational repression. Their discovery added a new dimension to the understanding of complex gene regulatory networks in humans and animals alike.
MicroRNA (miRNA) was initially discovered in Caenorhabditis elegans by Victor Ambros' laboratory in 1993 while studying the gene lin-14. At the same time, Gary Ravkun identified the first miRNA target gene. Those two groundbreaking discoveries identified a novel mechanism of posttranscriptional gene regulation.
However, the importance of miRNA was realized seven years later when Ravukon and Horvitz laboratories identified a second miRNA in the same model nematode species (named let-7), and when another class of short RNA (siRNA) involved in the process of RNA interference was discovered. Only then it became obvious that short non-coding RNA molecule identified in 1993 was part of a much bigger phenomenon.
Since then, an increasing number of miRNAs have been recognized in mammals. In humans alone over 700 miRNAs have been identified and fully sequenced, and the estimated number of miRNA genes in a human genome is more than one thousand. Based on computer models, miRNAs in humans have a direct influence on at least 30% of the genes in the whole genome.
The importance of microRNA
miRNAs represent small RNA molecules encoded in the genomes of plants and animals. These highly conserved 22 nucleotides long RNA sequences regulate the expression of genes by binding to the 3'-untranslated regions (3'-UTR) of specific mRNAs. A growing body of evidence shows that miRNAs are one of the key players in cell differentiation and growth, mobility and apoptosis (programmed cell death).
Differentiating miRNAs from other classes of small RNAs that are present in the cell is often cumbersome – particularly the distinction from endogenous small interfering RNAs (siRNAs). The most significant distinction between miRNAs and siRNAs is whether they silence their own expression. Almost all siRNAs (regardless of their viral or other origin) silence the same locus from which they were derived. On the other hand, most miRNAs do not silence their own loci, but other genes instead.
miRNAs regulate diverse aspects of development and physiology, thus understanding its biological role is proving more and more important. Analysis of miRNA expression may provide valuable information, as dysregulation of its function can lead to human diseases such as cancer, cardiovascular and metabolic diseases, liver conditions and immune dysfunction.
Last Updated: Jan 26, 2015