Saturday, September 6, 2008

Micro RNA and Gene Regulation

Ribonucleic acid (RNA) is a polymer of nucleotides in which each nucleotide unit consists of a ribose sugar, a nitrogenous base and a phosphate group. There are four types of nitrogenous bases namely, Adenine (A), Thymine (T), Guanine (G) and Cytosine (C). The base composition of RNA is similar to the DNA but not identical. The Thymine base present in DNA is replaced by Uracil in RNA.Unlike DNA, RNA in the cell is single stranded and do not exist as a helical structure. The genetic information from DNA is first transcribed (copied) to RNA strand and then the RNA strand is used as a template for protein translation. Of many types of RNA, some are involved in protein translation while others function as regulatory element. Micro RNA (miRNA) is one of the recently identified RNA elements involved in gene regulation.

miRNA is a short (19-23 nucleotides), single stranded, non-coding RNA (not translated into protein) which is known to be present only in eukaryotic organisms (organisms whose nucleus is separated from cytoplasm by nuclear membrane), till date. miRNAs are transcribed as part of a long RNA molecule called primary miRNA (pre-miRNA). This pre-miRNA is double stranded and by the action of ribonuclease (dicer) is converted into single stranded mature miRNA. After maturation each miRNA is bound by a complex (which is similar to the RNA induced silencing complex or RISC). Recently, it has been identified that miRNA down regulate (lower or stop) the expression of many genes. A very little is known on the miRNA based gene expression. miRNA is known to mediate gene regulation at translational level. During translation RISC bound miRNA binds to its specific mRNA sequence through sequence complementarity. Binding of miRNA to mRNA resulted in translational inhibition and mRNA degradation. The choice between translational inhibition and mRNA destruction is governed by the degree of mismatch between the miRNA and its target mRNA, with degradation being the outcome for best-matched targets. As miRNAs can inhibit the translation of imperfectly matched targets, it is possible that each miRNA may target multiple genes, and that several miRNAs may regulate a given target.


At present miRNA is of immense scientific interest for its regulatory function, especially in the field of cancer cell research. It is well-known that cell multiplication in the body is controlled by certain genes and any disability of these genes leads to the uncontrolled proliferation of cells which finally resulted in tumor or cancer. Therefore, it is not surprising to assume that miRNA might play a key role in cancer development. One cluster of miRNAs, known as mir-17–92, has been shown to be a potential oncogene in an in vivo model of human B-cell lymphoma. In another study (He et al. and O’Donnell et al.), it has been shown that a cluster of miRNAs on human chromosome 13 are regulated by c-Myc (a cancer promoting gene) gene and over expression of 6 miRNAs are linked to increased expression of c-Myc that results in cancer. Lu et al. has shown that expression of miRNA varies dramatically across tumour types and defines the cancer type (such as gastric, colon and liver cancer) more accurately than mRNA expression profile. This allowed scientists to use miRNA as diagnosis and therapeutic basis. The miRNA research is expected to provide invaluable information in the future therapeutics development for many diseases including cancer.

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