MicroRNA Applications, Essay Example

Introduction

MicroRNAs are RNAs which are which do not code for any protein and they occur naturally in nature. They are encoded by genes whose DNA undergoes transcription but are not translated in to proteins, as opposed to the other types of RNA, for example a messenger RNA will be transcribed in the nucleus and translated in to proteins in the cytoplasm. They are important in several biological processes and in development of various diseases. They are short types of RNA with most of them having about twenty one to twenty three nucleotides. Their origin is in the nucleus in the genome of the cell and they contain nucleic material just like any other nucleic acid molecule.

Formation and Processing Of MicroRNAs

They are formed from deoxyribonucleic Acids (DNA), from which a primary microRNA is formed, through a process called transcription. The Primary microRNA (also called the pri-microDNA) is further processed to form the Precursor microRNA (Pre-microRNA) is formed which has 70 nucleotides through a process termed as Drosha processing. This process requires a RNA which is single on both position 3’ and 5’ of the mother molecule. The Precursor microRNA is further refined, through a process termed as dicer processing and using an enzyme called the Dicer, to produce the final product, the microRNA strand. Both Drosha processing and the transcription take place in the nucleus but the Dicer processing takes place in the cytoplasm, after the precursor microRNA has been exported from the nucleus to the cytoplasm.  In Eukaryotes they are single stranded ribonucleic acid which regulates gene expression.  Mature microRNA is usually complementary to either one or more molecules of massager RNA. They regulate gene expression by inhibiting translation of a massager RNA which it is complementary with.

Functions of MicroRNAs

The major functions of microRNA are cell processes such as coordination of cellular division, apoptosis during development, resistance to stress of the cell, metabolism of fat and positive and negative regulation but mostly down regulation of gene expression. It has been postulated that MicroRNA genes are mostly located at fragile sites and regions of genomes involved in most cancers (Austin 2000). They are also the same regions where viruses and other carcinogenic agents attack the genome at. These ribonucleic acids regulate about half of the genes for coding proteins in humans by down regulating them. Therefore less than half of genes of a human are always down regulated. This indicates that they may have a role in cancer prevention. Therefore the precise role of the microRNAs is prevention of cancer development and other diseases. MicroRNAs can also cause gene activation.

MicroRNA and Diseases

The microRNA is involved in the normal functions of all the eukaryotic cells. However, in case of their deregulation, which can either be up regulation or down regulation they are associated with causation of diseases. In mice which were altered to produce c-myc protein (a protein associated with many cancers) in excess proved that microRNA has an important role in carcinogenesis. Mice that were made to produce an excess of certain types of microRNA which is usually found in lymphoma cells developed the lymphoma within fifty days and then died after two weeks. Interestingly, mice that did not have the excess to the microRNA lived for more than one hundred days. Leukemia also can be caused by inserting a viral nucleic acid next to 17-92 sequence of microRNAs causing the affected microRNA to express more. In another study, it was found that some two types of MicroRNA inhibit a protein called E2F1, which is involved in the regulation of proliferation of cells. The involved microRNA binds to the messenger RNA before its translation to proteins.

In addition to the usefulness of microRNAs in carcinogenesis, they are also useful in development of heart disease. This was discovered by maturation of microRNA of a Murine heart. This has established that these RNAs play an important role in the development of the heart. In specific heart diseases, expression levels of certain specific microRNAs change significantly in human hearts which are diseased and therefore reflecting their importance in the pathogenesis of various cardio-myopathies and also their causes. Some specific microRNAs play significant role in the development of a human heart, including regulation of important factors in cardio-genesis (the development of the heart). They are also involved in hypertrophy of the heart and in the cardiac conductance.  Lastly, microRNAs are implicated in the development of neurologic disorder call schizophrenia.

Clusters of MicroRNA

A microRNA cluster refers to two or more microRNAs which occur together on the same loci on the cell genome. Some of the clusters are, cluster one, and cluster two. Cluster one is usually located on chromosome nineteen and is only present on placenta only. This cluster is composed of about 54 microRNAs, which is the largest cluster ever to be discovered (Charles, 2009). Their expression goes hand in hand with stem cells of the human embryo they are highly expressed in a human embryo. It is only primates which have this cluster being conserved. The rest of the mammals do not have a conserved sequence. Cluster two is located on the X chromosome.  It is specifically located in the testis only and only in males. It has ten microRNAs, with primates having all of them being conserved, dogs having only seven of them conserved and four conserved in rats and mouse.

Significance of MicroRNA

Human genome has a total of over eight hundred microRNA with only four hundred to five hundred being conserved. There has been a lot of evolution which is unique to primates, with a discovery of eighty nine novel microRNAs. Again, under primates, there are about fifty three microRNAs which are not conserved (Jeans et al., 1990). Some of the microRNAs are involved in the carcinogenesis for example, 13q14 deletions of miR-15a and miR-16a are involved in chronic lymphocytic leukemia of B cell type, prostate cancer, and multiple myeloma and lymphoma for example mantle cell type. It has also been postulated that these microRNA are located in crucial loci of the human genome. They are mostly located in the regions of oncogenes which are the integration sites of Human Papilloma Virus (HPV), a virus which is known to be associated with many tumors like the cancer of the cervix (Lewis, 1977).

The virus causes rearrangements or deletions of these microRNAs there by interfering with the normal apoptosis of mutant cells and other cells. This leads to immortality of the cells and an uncontrolled cell proliferation, therefore resulting in to a tumor. The virus probably interferes with the production of the microRNA which is very useful in prevention of tumors and cancer. When the microRNAs production is interfered with, then the messenger ribonucleic acid translates, without a check and also inhibits apoptosis leading to accumulation of immortal cell, a process now referred to as carcinogenesis.

References

Austin, C.C. (2000). Genetics. New York, America: Educational publishers.

Charles, S.S. (2009). The Cell Biology. London: Swift Printing Press.

Jeans, C. V., John, B. & Charles, M. N. (1990). The Molecular Basis of Cancer. New York: Academic Publishing

Lewis, F. N.(1977). Genetics: A look at the RNAs. (C. Year Release) New York: Free Man Publishers.