RNA Interference

Introduction

Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are considered as the most important nucleic acids and this has been confirmed by many biologists. The nucleotide is the basic structural constitution of nucleic acid i.e. DNA and RNA. In RNA interference the small piece of RNA shut down the protein translation by binding mRNA that codes for those proteins. The particular mRNA codes for protein synthesis. RNA interference (RNAi) regulates the post-transcriptional mechanism of genes. In this process, small interfering RNAs (siRNAs) induce the sequence-specific degradation of homologous messenger (mRNA). RNA interference is widely used in research in biology as well as drug development for the last sixteen years. RNA interference is a process of biology that obstructs the target genes' genetic impression in plants and animals as well as in fungi. That is the reason, researchers called it a phenomenon of gene silencing.

RNA Interference Pathway

RNA interference is commonly observed in eukaryotic cells. Transcriptional and posttranscriptional RNA interference used double-stranded RNA (dsRNA) in the process. The RNA interference put off protein synthesis. Apart from these, it assists to arrest cancer, infection of the virus, and neurodegenerative diseases.

By natural or artificial method a long double-stranded RNA is inserted in a cell, and RNA interference takes place. The double-stranded RNA (dsRNA) split into small pieces with the help of enzyme dicers. The small fragments are microRNA (miRNA) and simple interfering RNA (si RNA). RNA polymerase (RdRP) is generated by double-stranded RNA. The gene silencing process can take place in two phases through RNA interference.

Phase I

Initiation

• The stage starts with the production of simple interfering RNA (si RNA). This stage further proceeds with the help of the type III endonuclease Dicer.

• Dicer enzymes are of two types namely Dicer-I and Dicer II. The dicer enzyme is also known as RNase III.

• Dicer I and Dicer II are homologous in structure but have different features like ATP requirement and substrate specificity.

MicroRNA (miRNA)

• The dicer-1 enzyme does not depend on its function on adenosine triphosphate.

• Dicer -1 utilizes its protein partner to bind double-stranded RNA.

• Dicer1 connects with dsRBD within a protein known as loqs found in drosophila. The dsRBD is the domain of double-stranded RNA.

• The loqs protein that is present in miRNA activates its function and gives direction to the specific activity that processes miRNA.

• As a result of this gene expression is controlled by microRNA (miRNA).

• The loqs encode three dsRBD which have the ability to generate two types of proteins namely PA and PB.

• The PB proteins increase the affinity of DC1 towards the miRNA precursor.

Simple interfering RNA (si RNA)

• The Dicer-2 enzyme depends on adenosine triphosphate.

• It also exhibits substrate specificity towards double-stranded RNA (dsRNA).

• Structurally Dicer-2 is almost similar to Dcr 1.

• Dicer-2 also needs double-stranded RNA (dsRNA) binding proteins.

• R2D2 is a protein.

• The heterodimeric complex is formed when R2D2 functions in a combination with the specific enzyme RNase.

• The R2D2 is constituted of one double-stranded RNA (dsRNA) binding domain.

• These results show that both the dsRNA binding domains of R2D2 and Dicer-2 are required for the R2D2 and Dicer-2 complex.

• The dsRNA bind siRNA into a si-RNA-induced silencing complex (siRISC).

Phase II

The Effector

• In RNA interference next phase is the involvement of guide strand incorporation.

• The guide strands are single strands and constitute microRNA (miRNA) and simple interfering RNA (si RNA).

• Either RNA-induced initiation of transcriptional gene silencing (RITS) or the RNA-induced silencing complex (RISC) is the effector complex in stage II.

RISC

• RNA-induced silencing complex is the full form of RISC.

• RISC is the PPD protein of PAZ PIWI domain.

• The PIWI is constituted of three hundred amino acids and is placed in the C terminal in the complex of protein.

• The PAZ constituted only a hundred amino acids and is placed centrally in the complex of protein.

• In nematodes, arthropods as well as in Chordata the PPD proteins involved in si- RNA-induced silencing are Agro2 and hAgro2.

• These proteins are efficient in performing siRNA-mediated mRNA cleavage.

Small variations in siRNA structure affect the RISC complex which is proven by scientists. For specific gene silencing, a small amount of stimulation is enough for more entire organisms. The signal intensity can be amplified through RNAi silencing mechanism.

RNA Interference Application

The RNA interference application are listed below −

• Gene Knockdown − Generally RNA interference is used to study the activity of genes in culture cells and model species. It is also used to bring down the aspects of targeted genes.

• Functional Genomics − This technique helps in studying the gene mapping of annotation in plants. Apart from these, it is also used in the study of bread wheat.

• Applications in the Medical Field − RNA interference assists to arrest cancer, infection of the virus, and neurodegenerative diseases. RNA interference is also used in the treatment of bacterial, viral, and parasitic infections. It can also subside pain and regulate sleep.

Conclusion

In RNA interference, a small piece of RNA shut down the protein translation by binding mRNA that codes for those proteins. The particular mRNA codes for protein synthesis. RNA interference (RNAi) regulates the post-transcriptional mechanism of genes. In this process, small interfering RNAs (siRNAs) induce the sequence-specific degradation of homologous messenger (mRNA). RNA interference is widely used in research in biology as well as drug development for the last sixteen years. RNA interference is commonly observed in the eukaryotic cells.

FAQs

Q1. What are the functions of ribonucleic acid?

Ans. The main function of ribonucleic acid is protein synthesis. Apart from these ribonucleic acid conveys genetic information which is translated by ribosomes into different types of proteins. The three different types of RNA i.e. mRNA, tRNA, and rRNA are used in the process of protein synthesis.

Q2. What do you understand by eukaryotic transcription?

Ans. This type of transcription also involves four steps i.e. binding, initiation, elongation, and termination. In this type, transcription takes place in the presence of transcription factors. Based on the genes there are various types of RNA polymerase molecules that can transcribe the DNA.

Q3. What is translation?

Ans. When mRNA message code is translated to protein then that is known as translation.

Q4. What do you understand by adenosine triphosphate?

Ans. Adenosine triphosphate is commonly known as ATP. In eukaryotic cells, adenosine triphosphate is the main source of energy. This energy is either reserved or used in various cellular activities in the cells.

Q5. What do you understand about neurodegenerative diseases?

Ans. Neurodegenerative disease is a disorder of the nervous system. It is not curable and it slowly damages the nerve cells. The symptoms vary from person to person. Generally, it effects the movement of the body as well as the function of the brain.