Gene expression in tissues and cells of every complex organism is precisely controlled and greatly dependent on different conditions such as changes in the environment, development, drugs or diseases. Various cells and organ systems within such organisms, to include people, contain different gene expression profiles, therefore appropriate understanding of regulatory mechanisms involved in such expression represents one of the main issues in genomic medicine.
A micro RNA (miRNA) is a small non-coding RNA molecule (containing about 22 nucleotides) found in plants, animals, and some viruses, which functions in RNA silencing and post-transcriptional regulation of gene expression.
Non-coding RNA molecules have a role in a plethora of regulatory events, from controlling the number of copies in bacterial division to X-chromosome inactivation in mammals. Recent analyses of the animal and human genomes have shown that the majority of RNA transcripts do not code for proteins, meaning they are messenger RNA's or mRNA's, yet are instead non-coding RNA's or, 'ncRNA's.'
MicroRNA's or, 'miRNA's,' comprise a novel class of small, non-coding endogenous RNA's that regulate gene expression by directing their target mRNA's for degradation of translational repression. Their discovery added another new dimension to the understanding of complex gene regulatory networks in animals and people alike.
The Discovery of MicroRNA
MicroRNA or, 'miRNA,' was initially discovered in, 'Caenorhabditis elegans,' by Victor Ambros' laboratory in the year 1993 while studying the gene, 'lin-14.' At the same time, Gary Ravkun identified the first miRNA target gene. The two groundbreaking discoveries identified a novel mechanism of post-transcriptional gene regulation.
The importance of miRNA; however, was realized seven years later when Horvits and Ravukon laboratories identified a second miRNA in the same model nematode species named, 'let-7,' and when another class of short RNA or, 'siRNA,' involved in the process of RNA interference was discovered. Only at that time did it become obvious that short non-coding RNA molecules identified in 1993 were part of a far larger phenomenon.
Since that time, an increasing number of miRNA's have been recognized in mammals. In people alone more than seven-hundred miRNA's have been identified and fully sequenced and the estimated number of miRNA genes in a human genome is more than one-thousand. Based upon computer models, miRNA's in people have a direct influence on at least thirty-percent of the genes in the entire genome.
How Important is microRNA?
MiRNA's represent small RNA molecules encoded in the genomes of animals and plants. The highly conserved twenty-two nucleotides long RNA sequences regulate the expression of genes by binding to the untranslated regions of specific mRNA's. An increasing body of evidence reveals that miRNA's are one of the key players in cell differentiation and growth, mobility and, 'apoptosis,' or programmed cell death.
Differentiating miRNA's from other classes of small RNA's which are present in the cell is often times cumbersome, especially the distinction from endogenous small interfering RNA's or, 'siRNA's.' The most significant distinction between miRNA's and siRNA's is whether they silence their own expression. Nearly every siRNA – despite their viral or other origin, silence the same locus from which they were derived. On the other hand, the majority of miRNA's do not silence their own loci, but other genes instead.
MiRNA's regulate diverse aspects of physiology and development, therefore understanding its biological role is proving to be increasingly important. Analysis of miRNA expression might provide valuable information as dysregulation of its function can lead to human diseases such as cardiovascular and metabolic diseases, cancer, immune dysfunction and liver conditions.
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