Mirna Notes

MiRNA (or micro RNA) is a non-coding RNA molecule that is typically single-stranded and approximately 22 nucleotides in length. It is involved in the regulation of gene expression and gene silencing, and is found naturally in plants, animals, and some viruses.

miRNA was first discovered by Ambros, Lee, Feinbaum and their group. They found that miRNAs are present in various types of mammalian cells, as well as circulating in extracellular fluids such as blood and cerebrospinal fluid.

miRNA and mRNA interact through base pairing, allowing miRNA to silence genes. This can be done either by cleaving or destabilising mRNA, or by reducing the efficiency of translation.

miRNA Biogenesis

Small non-coding RNAs, such as microRNA (miRNA), small interfering RNAs (siRNA), and piRNA, have recently been discovered to have a role in the regulation of gene expression, RNA processing, transcription, translation, and RNA stability.

miRNA is a single-stranded RNA molecule, typically 21-25 nucleotides in length. It is transcribed by RNA polymerase II and III, and is initially transcribed as a long pre-miRNA. This pre-miRNA undergoes cleavage and processing to form a mature miRNA. Additionally, many miRNA genes are found in the introns of other genes. The pre-miRNA is much longer than the mature miRNA, and includes a 5’ cap and 3’ poly(A) tail.

The pre-miRNA undergoes processing in both the nucleus and cytoplasm. It is derived from the hairpin loops in the pre-miRNA transcripts. In the nucleus, the pre-miRNA is processed by the enzyme Drosha, which has an RNase III domain to form a microprocessor complex.

In the cytoplasm, pre-miRNA is processed by another enzyme called Dicer. It is also an RNase III enzyme. It forms a miRNA duplex of 22 nucleotides. Either of the strands has the capability to act as a miRNA. In the RISC complex, only one strand is incorporated that targets the mRNA.

In plants, the biogenesis process differs from that of animals, as Dicer homolog is responsible for both inside and outside nucleus processing.

Mechanism of Action

miRNA, like siRNA, is involved in gene silencing through RNA interference. It is particularly involved in post-transcriptional gene silencing (PTGS).

The mature miRNA is associated with other proteins to form the RNA-Induced Silencing Complex (RISC), also referred to as miRISC. Processing of pre-miRNA by Dicer causes the duplex to unwind and only one miRNA strand is associated with the RISC complex, while the other strand is generally degraded.

miRNA silences a gene by either degrading mRNA or inhibiting the translation. It also destabilises mRNA by shortening the poly(A) tail.

Function and Application

The main function of miRNA is gene regulation. In animals, miRNA is generally complementary to the 3’ untranslated regions of mRNA, while in plants, miRNA is complementary to the coding regions of mRNA.

In plants, base pairing is nearly perfect and it induces cleavage of mRNA. In animals, it is partially complementary to mRNA and inhibits mRNA translation and inhibits the synthesis of a gene product. It can also induce mRNA deadenylation leading to destabilisation of mRNA.

miRNA can also affect the expression of genes by methylation of DNA at the promoter site, as well as causing histone modifications.

MiRNAs are highly conserved across species during evolution, making them useful phylogenetic markers. Furthermore, they are capable of targeting multiple genes and are essential for the normal functioning of a cell and gene regulation.

miRNA have been found to play a role in the regulation of the blood coagulation cascade and hemostasis, as well as in the regulation of obesity, diabetes and insulin resistance. One class of miRNA has been observed to increase with age, and this accumulation has been linked to insulin resistance and the development of obesity and diabetes.

They regulate the genes involved in cell cycle, cell signalling, apoptosis, nervous system development, etc. and are involved in the altered gene expression during addiction.

Many diseases, including Alzheimer’s, schizophrenia, depression, and anxiety disorders, have been found to have an altered miRNA expression. miRNA is also involved in the regulation of cholesterol metabolism and can be found in cardiomyopathies during cardiovascular diseases and stroke.

MiRNA dysregulation has been associated with a variety of inherited diseases, such as cataract, progressive hearing loss, skeletal and growth defects, as well as chronic lymphocytic leukemia (a type of cancer) and colorectal cancer. Additionally, the interaction of miRNA with the tumour suppressor gene has been linked to the proliferation of hepatocellular carcinoma cells.

miRNA is known to act as a tumour antagonist and can be used as targets or tools for cancer treatment. It has been shown to regulate many genes involved in DNA repair, and when the DNA repair mechanism is defective, it can lead to an accumulation of mutations and cancer. Abnormal expression of miRNA genes involved in DNA repair has been linked to various types of cancer.

Viral miRNA plays a pivotal role in gene regulation of both viruses and hosts, which ultimately benefits the virus. It is essential for the pathogenesis of viral diseases.

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