microRNA

09.10.2024

microRNA

 Why in the news?   

The 2024 Nobel Prize in Physiology or Medicine was awarded to American biologists Victor Ambros and Gary Ruvkun by the Nobel Assembly at Karolinska Institute in Stockholm, Sweden.

The scientists won the esteemed prize for the discovery of microRNA and its role in post-transcriptional gene regulation.

What are microRNAs?

• Gene expression in cells and tissues of every complex organism is precisely controlled and largely dependent on different conditions (such as development, changes in the environment, diseases or drugs).
• Various cells and organ systems within such organisms (including humans) contain different gene expression profiles.
• Thus, proper understanding of regulatory mechanisms involved in such expression represents one of the key issues in genomic medicine.

Non-coding RNA (ncRNAs):

• These molecules have a role in a plethora of regulatory events - from controlling the number of copies in bacterial division to X-chromosome inactivation in mammals.
• Recent genomic scans of humans and animals have revealed that the majority of RNA transcripts are ncRNAs rather than messenger RNAs (mRNAs), which code for proteins.

About miRNAs:

MicroRNAs/ miRNAs are small, non-coding molecules of RNA, which plays an important role in determining how much mRNA, which carries genetic information, eventually gets translated into protein.

Significance of miRNA:

The body makes proteins in a complex process with two broad steps.

• In the transcription step, a cell copies a DNA sequence into mRNA in the nucleus. The mRNA moves from the nucleus, through the cell fluid, and attaches itself to the ribosome.
• In the translation step, another type of RNA called transfer RNA (tRNA) brings specific amino acids to the ribosome, where they are linked together in the order specified by the mRNA to make the protein.
• miRNA regulates the production of proteins by bonding with and subsequently silencing the mRNA at an appropriate juncture. The process is called post-transcriptional gene regulation.

Discovery of miRNAs:

• It was initially discovered in a tiny roundworm (C. elegans) by Victor Ambros' laboratory in 1993 while studying the gene lin-14. At the same time, Gary Ravkun identified the first miRNA target gene.
• These two groundbreaking discoveries identified a novel mechanism of posttranscriptional gene regulation.

Why were scientists honoured?

• The scientists were honoured for their discovery of a fundamental principle governing how gene activity is regulated.
• Gene regulation is a process that helps each cell pick the right tools for its specific tasks.
• Their research led them to the discovery of microRNA, which provided a whole new way of understanding how bodies of complex organisms such as humans function.

Understanding the role of miRNA:

• Genetic information is stored in DNA inside the nucleus of each cell.
• This information is copied to mRNA, which carries the instructions for protein synthesis.
• Different tissues in the body create specific proteins based on their functions, such as making muscles contract and helping nerves communicate.
• Cells differentiate and perform their tasks through gene regulation, which turns specific genes on or off.
• Errors in gene regulation can lead to serious diseases, including cancer, diabetes, autoimmune conditions, etc.
  • Hence, understanding gene regulation is essential for understanding and potentially treating these diseases.

• A single micro-RNA can regulate the expression of many genes, and alternatively a single gene can also be controlled by multiple micro-RNAs.
  • This leads to fine tuning of different types of cells despite similar genetic information.

Nobel-winning research: a brief history

• Ambros and Ruvkun studied a roundworm, Caenorhabditis elegans which, despite its small size, had specialized cell types such as nerve and muscle cells.
• Ambros and Ruvkun studied two mutant strains, lin-4 and lin-14, both of which exhibited abnormalities – their genetic programming that controls development was not functioning as expected. Ambros’ previous research proved that lin-4 suppressed the activity of lin-14, but could not tell how it did so.
• The biologists individually researched how lin-4 affected the activity of lin-14. Ambros analyzed the lin-4 mutant and cloned the gene and found out that it produced an unusually short RNA molecule that lacked a code for protein production. The findings suggested that this small RNA molecule could be responsible for inhibiting lin-14.
• Around the same time, Ruvkun investigated the regulation of the lin-14 gene in his lab and found that lin-4 did not block the production of lin-14 mRNA. Since the late 1960s, gene regulation has been understood as a process that determines which mRNAs are produced, and hence, how genetic information flows. Ruvkun found that the regulation of lin-14 mRNA occurred later in the gene expression process by inhibiting protein production.
• Ruvkon’s experiment also revealed an important segment in the lin-14 mRNA that was essential for its inhibition by lin-4. The short lin-4 sequence that Ambros discovered in his research matched complementary sequences in the critical segment of the lin-14 mRNA, which means that they can pair together like keys fit into locks.
• The two biologists conducted further experiments and found that lin-4 microRNA, the “unusually short” RNA molecule, attaches to lin-14’s mRNA and blocks the production of lin-14 protein. This is how microRNA was discovered.
• The results were not enthusiastically accepted by scientists as the behaviour was thought to be specific to C. elegans, and therefore irrelevant to complex animals. However, in 2000, Ruvkun’s research group published discovery of another microRNA, encoded by the let-7 gene. The let-7 gene is present throughout the animal kingdom.

Applications

• A single micro-RNA can regulate the expression of many genes, and alternatively a single gene can also be controlled by multiple micro-RNAs. This leads to fine tuning of different types of cells despite similar genetic information.
• Abnormal regulation by microRNA can contribute to cancer, and mutations in genes coding for microRNAs have been found in humans, causing conditions such as congenital hearing loss, eye and skeletal disorders.

                                                                Source: The Hindu

Consider the following statements regarding microRNA (miRNAs):

1. They are a class of non-coding RNAs that play important roles in regulating gene expression.

2. If the level of a particular microRNA is underexpressed, the protein it normally regulates will also be underexpressed.

Which of the statements given above is/are correct?

A.1 only

B.2 only

C.Both 1 and 2

D.Neither 1 nor 2

Answer A