Nobel Prize in Medicine for microRNA

Syllabus:

  • GS 2: Health
  • GS 3: Achievements in Science and technology.

Why in the News?

Victor Ambrose and Gary Ruvkun won the Nobel Prize in Physiology or Medicine for the discovery of microRNAs, which fundamentally changed our knowledge of gene regulation in human body.

Nobel Prize in Medicine for microRNA

Introduction

  • Revolutionary discovery of microRNAs (miRNAs) by Victor Ambrose and Gary Ruvkun revolutionized our understanding of gene regulation.
  • Their study revealed a new mechanism by which cells regulate protein synthesis in human body, highlighting the important role of miRNAs in various biological processes and diseases.

Breakthrough discovery of mRNA

  • Post-doctoral researchers Victor Ambrose and Gary Ruvkun in December 1993, published ground-breaking papers in the journal Cell.
  • Their study showed how the roundworm Caenorhabditis elegans uses small RNA molecules to regulate protein synthesis.
  • At first, the scientists thought this process unique to mosquitoes and not relevant to other living creatures.

Shifting paradigm

  • 7 years later, Ruvkun discovered that this mechanism of gene regulation, which includes microRNAs, exists throughout the animal kingdom.
  • This revelation revolutionized molecular biology, demonstrating the critical importance of microRNAs in gene regulation and their potential implications for human health.

Awarded Nobel Prize

  • Last week, Ambrose and Ruvkun were awarded the Nobel Prize in Physiology or Medicine for their discovery of the universal role of microRNAs in gene regulation.
  • Their work continues to stimulate research into the role of microRNAs in health and disease, marking a milestone in molecular biology.

Process of Protein Synthesis

Role of DNA

  • Every cell in the organism contains DNA, which is the blueprint for the construction and maintenance of the organism.
  • DNA provides instructions for making proteins, which carry out most of the functions of the cell.
  • Proteins perform specific functions; For example, haemoglobin carries oxygen to the blood.

Function of Gene and Protein in human body

  • Human DNA contains between 19,000 and 20,000 genes, and each gene contains the instructions for making a specific protein.
  • Although all cells have the same genes, they produce only the proteins needed for the cell to function.
  • For example, red blood cells produce hemoglobin, but stomach cells do not.

mRNA and Transcription

  • When a cell needs to make a protein, it temporarily makes a copy of a gene called messenger RNA (mRNA).
  • This process, called transcription, converts information from DNA into an mRNA sequence.
  • mRNA then directs the cell to make protein, but this process must be regulated to avoid harmful overproduction of proteins.

Protein synthesis Regulation

  • Synthesis of Protein continues, until it is stopped. Unregulated protein may result in excess protein waste or harm.
  • Protein synthesis was once thought to cease only when the mRNA was destroyed or degraded, either by certain enzymes or because of instability.

microRNAs (miRNAs) Discovery

  • Gary Ruvkun and Victor Ambrose discovered a new regulatory mechanism in cells.
  • They discovered microRNAs (miRNAs), small RNA molecules that bind to mRNAs and prevent them from becoming proteins.
  • Part of the process of post-transcriptional gene organization is the binding and inhibition of protein synthesis.

How microRNA functions?

  • In terms of Pharmacology, microRNAs (miRNAs) are synthesized using the same process as messenger RNAs (mRNAs), both of which are 4 chemicals organized on a sugar-phosphate backbone
  • The difference lies in their size: mRNA ranges from 100s to millions of bases, while miRNAs are typically only 22 bases long.
  • The sequence of the miRNA base complements the sequence specificity on the target mRNA.
  • Once bound to its target, the miRNA marks the mRNA for degradation or prevents it from acting as a template for protein synthesis, effectively halting protein synthesis.
  • This mechanism allows miRNAs to inhibit protein synthesis before it begins, ensuring proper regulation.
  • Since Ruvkun discovered the first human miRNA in 2000, thousands of miRNAs have been found to regulate about 60% of human genes.

Significance of miRNAs in cell behaviour

  • Regulation of protein synthesis is critical for normal cellular function.
  • miRNAs are important in processes such as animal growth, cell differentiation, cell division, and cell death.
  • They also play an important role in the body’s response to stress and disease, including cancers.

mRNAs Potential in Targeted therapy

  • The high specificity of miRNAs makes them ideal candidates for targeted therapy, especially for diseases such as cancer involving abnormal protein synthesis.
  • Despite therapeutic potential, research into the clinical utility of miRNAs has faced initial challenges, resulting in a slow start to realize their full therapeutic value.

Future outlook

  • Scientists were inspired by the 1st miRNA experiments in mice, experiment found miRNAs effectively suppressing the development of lung tumours.
  • 1st human trials of miRNA-34a began in 2013, but the technology to deliver miRNAs to target cells was not yet developed.
  • Very high doses were used to ensure that the miRNA reached the target site, triggering an immune response. When 4 patients died, the trial was terminated.

Success in miRNA Delivery

  • Subsequently significant advances were made in miRNA delivery systems, allowing scientists to test other miRNAs for liver disease, various cancers and certain cardiovascular diseases.
  • As of last week, 581 clinical trials involving miRNAs had been registered in the US, of which 215 had been completed and 20 abandoned due to safety concerns.
  • Despite the obstacles, the therapeutic potential of miRNAs remains promising, although there are new approaches for many conditions.
  • Ambrose and Ruvkun received the Nobel Prize for the critical role of miRNAs in gene regulation and cellular processes, although they still have broad medical applications.

RNA analysis and Nobel Prize

  • This is the 5th Nobel Prize for RNA research, after mRNA vaccines (2023), RNA interference (2006), RNA as an enzyme (1989), and the discovery of mRNA (1965).
  • The importance of RNA is increasingly recognized over DNA, as RNA plays a critical role in maintaining the delicate balance of cells, highlighting the complexity of miRNA research.

Conclusion

Discovery of microRNAs revolutionized molecular biology and offered a new perspective on gene regulation which can provide therapies for complex diseases such as cancer may be possible with the help of miRNA delivery.

Source:The Hindu

Mains Practice Question:

The discovery of microRNAs changed our understanding of gene regulation. Discuss the importance of microRNAs in the regulation of gene expression and their potential applications in human health and disease prevention.