What Are Micro RNA

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What are micro RNAs?

Micro RNAs (miRNA) are small non-coding RNAs that are involved in regulating the translation of messenger RNA (mRNA). Over 1000 miRNAs have been identified which control approximately 60% of the protein coding genes1. The miRNAs are on average 23 nucleotides long, with nucleotides 2-7 acting as the seed region. The seed region is needed for specific mRNA interactions and mutations occur in this region it can disrupt the miRNA, mRNA Watson-Crick base pairing2.

mRNA is stabilized in the cytoplasm by adding a 5’ cap and a 3’ poly adenine tail, which prevents degradation by ribonucleases. The binding of miRNA can cause 3 events to occur; deadenylation, decapping, and 5’ to 3’ degradation1. Often in the 3’ untranslated region (UTR) there are AU rich elements (AREs) when the miRNA along with Argonaute 1, Argonaute 2 and Dicer1 is bound it allows rapid decay of the mRNA

1.2. miRNA biogenesis

miRNAs can be transcribed from their own genes; often there are clusters of these miRNA genes for example, C19MC, which is the largest human cluster3. Another place where miRNAs are coded for is within introns of other genes. The miRNAs are transcribed using either RNA polymerase II or III4,5, this is dependent on the specific promoter or terminator sequences for each gene. The new transcript is called the primary miRNA (pri-miRNA) and must undergo processing before it is able to regulate mRNA.

While in the nucleus the pri-miRNA undergoes the first cleavage, which is catalysed by Drosha, figure 1. Drosha is part of the RNase III family of enzymes and cleaves the transcript 11 base pairs from the double stranded/single stranded RNA junction3. For the cleavage to be accurate a molecular ruler in the form of Pasha (p...

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...t leads to a truncated TRBP. Cell lines that exhibited this mutated TRBP also had extremely low levels of Dicer. When wild type TRBP was restored to the cancer cell lines, Dicer expression increased to WT levels16. A study into nearly 300 primary human colorectal (sporadic or familial) or gastric (sporadic) cancers, from these 25.4% presented the mutant TRBP, and it was highest in familial colorectal cancers at 43.3%16.

1.4. Angiogenesis

The process of angiogenesis is the development of blood vessels. It is vital for all higher organisms, as oxygen is not able to diffuse throughout the body, but must be carried to cells far from the lungs.

One of the main system that controls angiogenesis and the maintenance of the blood vessels is angiopoietin-TIE17. TIE1 and TIE2 are tyrosine kinase receptors that have extracellular domains similar to that of EGF and Ig18.

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