MicroRNA (miRNA)
miRNA Formation and Function
Formation
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Nucleus
- MicroRNAs are first transcribed from genes as primary transcripts (pri-miRNA) by RNA Polymerase II.
- pri-miRNAs contain an adenosine tail and a 5' cap.
- The pri-miRNA is then processed by the microporcessor complex, containing the nuclease Drosha (a kind of RNase III) and the binding protein Pasha, into a ~65-nucleotide hairpin known as pre-miRNA.
- The pre-miRNA is transported out of the nucleus to the cytoplasm by the exportin-5 nuclear export factor and RAN-GTP.
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Cytoplasm
Function
- In a process similar to RNA interference (RNAi), the miRNA-RISC complex interacts with one or more mRNA for which the miRNA is partially complementary. The binding of the miRNA-RISC complex blocks translation of the mRNA, preventing expression of that particular gene. The miRNA-RISC complex can also initiate the degradation of the bound mRNA. Thus, miRNA is vital to gene regulation.
Structure
There is no specific crystal structure for miRNA because miRNAs are simply very short RNA strands. They are ~22 nucleotides in length and are of the same structure as other ssRNA molecules. Here is a basic graphic description of an RNA molecule. miRNA would be the same structurally, but would contain nucleotides specified by the gene from which it was transcribed.
Connections to Human Disease
miRNA has been shown to be linked to cancer development and tumorigenesis. Because miRNA is vital to gene regulation, an overabundance or underabundance of miRNA in the cell may have negative impacts and lead to the formation of a tumor. If there is an overabundace of a miRNA that regulates the expression of a tumor suppressor, tumorigenesis may occur because there is no protein to stop it. If there is an underabundance of a miRNA that regulates the expression of a proto-oncogene (a cancer-causing agent), tumorigenesis may occur because the proto-oncogene will be overly expressed. Below is a graphic representation of miRNA expression leading to tumorigenesis.
Studies have also showed links between miRNA and heart disease. Again, an overexpression or underexpression of miRNA can lead to major problems- heart failure, dilated cardiac myopathy, cardiac hypertrophy- in the heart. One study shows that an underexpression of miRNA arising from a decrease in cardiac Dicer endonuclease was characteristic of ailing and failing hearts. Another shows that an overexpression of certain stress-induced miRNA in the heart can lead to cardiac hypertrophy (a thickening of the heart muscle) and heart failure.
miRNA has been implicated in the expression of ~70 other human diseases. For more information on miRNA connection to human disease, visit the Human miRNA and Disease Database (HMDD). HMDD was compiled from the results of nearly 100 papers and is maintained by researchers at Peking University in Beijing, China.
Therapeutic Functions
miRNA's use in therapeutic treatments for human disease is one of the newest and fastest growing fields in modern medicine. There is an enormous amount of hope that miRNA's ability to regulate gene expression may be harnessed to alter the genetic pathways essential to the proliferation of many of the most devastating human diseases.
miRNA's relation to disease is defined by its upexpression and downexpression in connection with certain diseases. Scientists have been able to modify organisms to respond to the upexpression or down expression of certain miRNAs. This is a promising method of using miRNA in response to diseases such as cancer.
miRNA has also been found to be very important in the diagnosis of cancer. miRNA may be used to differentiate tumors and identify tumor origins. Because of miRNA's short length, it is highly unlikely to cleave itself, as larger RNA will do. Thus, miRNAs have a much longer shelf-life than other types of RNA, making them a potentially very useful tool in the diagnosis and understanding of cancer origins.
Comments (1)
Christopher Korey said
at 8:46 am on Apr 7, 2009
Looks good. As you convert the outline to text, Remember to be concise about each subsection and provide link outs to other pages or papers that provide more in depth detail if that is required. If someone wants more information give them a way to find it not necessarily put it on the page. I would remove the first section that describes the central dogma and just refer to the place where micro RNAs modulate gene expression. I would remove the first figure also. Try to divide the sections by inserting a horizontal bar. Remember to reference just like any other paper, images as well. For all the references you have make them links using the URLs that you have placed in there.
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