Core Concepts – RNA Interference
In this article, you will be able to understand how RNA interference works, and its benefits for human research.
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What is the RNA Interference?
RNA interference is a ribonucleic acid molecule that inhibits the expression of particular genes using established processes. The RNA interface process is natural.
During the last few years, RNA interference (RNAi) has become very popular as a natural mechanism for slicing gene expression. This tool makes it possible to specifically suppress a certain function on any target cell. The discovery of specific genes that have a role in disease processes is thought to benefit greatly from the use of RNAi technology.
Overall, two types of small RNA fragments allow RNA interference:
- Small interfering RNA (siRNA): Highly specific tool. Particularly synthesized to help decrease the translation of some messenger RNA (mRNA), to reduce specific proteins. When double-stranded RNA molecules are translated, siRNA is formed, and then they are size-cut in the nucleus before being released into the cytoplasm.
- Micro interfering RNA (miRNA): General suppressive tool. Formed by precursor single-stranded RNA, it also has a distinctive hairpin shape.
Although both of these RNA types are around 22 nucleotides long, they differ in their level of specialization and how they are synthesized.
How RNA interference works
RNAi always works the same way, regardless of the use of siRNA or miRNA. Four simple steps can summarize this process.
- The enzyme drosha (RNase) processes a large double-stranded RNA within the cell nucleus. A smaller dsRNA is produced, which is then exported to the cytoplasm. The dsRNA attaches to the dicer enzyme, which then cuts it into siRNA or miRNA.
- siRNA or miRNA molecules connect to a protein complex and activate it. This complex is mostly the RNA-induced silencing complex or RISC.
- Now, the siRNA or miRNA can bind to any target mRNA and prevent the further synthesis of proteins.
- These molecules achieve this by marking the mRNA for destruction. The cell then breaks it down.
RNAi can also help on protecting cells from viruses. In this process, they attack viruses’ mRNA and could even attack their genome before viral proteins are released.
RNA interference History
RNAi is considered to be one of the biggest and greatest discoveries in molecular biology during the last decades. This technology was first discovered in plants, called post-transcriptional gene silencing (PTGS). Later the process was found in all eucaryotes.
The RNAi phenomenon was first discovered in 1990 by Napoli and Jorgensen. They achieved this discovery while studying if chalcone synthase (a key enzyme in flavonoid biosynthesis) was a rate-limiting in anthocyanin synthesis.
The discovery of the RNAi process received the 2006 Nobel Prize in Physiology.
Biotechnological applications of RNA interference
Many areas have benefited from RNAi’s work, such as the food and medical industry. The most popular biotech products, created by RNAi, are nicotine-free tobacco, decaffeinated coffee, and nutrient-fortified foods.
Medical Industry
- Cancer: Research has shown that by targeting cancer-related genes, RNAi treatment would be a more specific, and less invasive, method than chemotherapy to treat cancer tumors. RNAi treatments could also help inhibit cancerous-cell migration.
- Neurodegenerative diseases: Studies in mouse have shown that by targeting the genes that produce Amyloid beta with RNAi, the amount of Aβ peptide reduces. This peptide is highly correlated to Alzheimers Disease.
- Viral infections: There are two strategies for antiviral treatments using RNAi. The first one consists on targeting viral RNAs. Studies that have applied this technique ere able to suppress viral replication of HIV, HPV, RSV, SARS-CoV, and others. The second strategy consists on blocking the initial viral entry by targeting host cells.
Food Industry
- Transgenics: RNAi has helped to lower natural plants toxins by genetic engineering. It has also been used to fortify, with antioxidants, and reduce levels of allergens in tomato plants.
- Crops: Certain gene sequences in insects have been impacted by crop modifications that express dsRNA. Other approach using dsRNA, without genetic engineering, is to add it on irrigation waters. This dsRNA will poison insects when they try to feed off the crop.
Other RNA-based therapeutics
Gene treatments have recently gained a lot of popularity. These treatments mostly make use of RNAs. RNA-based therapeutics have encountered significant challenges in the establishment of intracellular trafficking and bioactivity. While some RNA-based medicines are currently being studied or in preclinical studies, others have already received medical approval. One of the most popular therapy is CRISPR-Cas9.
CRISPR-Cas9
Clustered Regularly Interspaced Short Palindromic Repeat or just CRISPR has transformed scientific research and might soon lead to therapeutic discoveries that have never been possible due to biological advancements, just like genetic engineering. Cas9 is the enzyme in charge of cutting the DNA in a specified location (specified by guide RNA). CRISPR-Cas9 consists of cutting DNA and then letting the own DNA repair itself.
Other
Some of the clinically approved RNA-based drugs are:
- mRNA-1237, this drug targets the spike protein of SARS-CoV-2 (Covid-19)
- BNT162b1 and targets the RBD (receptor-binding domain) of Spike glycoprotein
- Patisiran, which uses siRNA molecules and targets polyneuropathy, causes the hereditary transthyretin-mediated amyloidosis disease
- Girosian also uses siRNA molecules and targets ALAS1 (Delta-aminolevulinate synthase 1) for the AHP disease (Acute hepatic porphyria)
- Pegaptanib uses an Aptamer molecule and targets VEGF (Vascular endothelial growth factor) for AMD disease (Age-related macular degeneration)