Why in the News?
In an exciting announcement from the Nobel Assembly at the Karolinska Institute in Stockholm, Sweden, American biologists Victor Ambros and Gary Ruvkun were awarded the 2024 Nobel Prize in Physiology or Medicine. These scientists were honored for their discovery of microRNA and its vital role in post-transcriptional gene regulation.
What’s in Today’s Article?
- What are microRNAs?
- How do miRNAs Control Gene Expression?
- The 2024 Nobel Prize in Physiology or Medicine
What are microRNAs?
Background: The expression of genes in every complex organism, including humans, is a carefully regulated process. This regulation depends heavily on various factors such as development, environmental changes, diseases, or drugs. Each cell and organ system has its unique gene expression profile, which must be tightly controlled for the organism to function properly. Understanding how this regulation works is one of the fundamental challenges in genomic medicine.
Non-coding RNAs (ncRNAs): Within the cells, there are molecules known as non-coding RNAs (ncRNAs) that are responsible for numerous regulatory events—ranging from bacterial division to inactivating the X-chromosome in mammals.
Modern genomic studies have revealed that most RNA transcripts in humans and animals are actually ncRNAs, not messenger RNAs (mRNAs), which are responsible for encoding proteins.
About mRNAs:
MicroRNAs, or miRNAs, are a specific type of small, non-coding RNA. Their function is crucial—they help determine how much of the mRNA, which carries genetic instructions, gets translated into proteins.
Production of mRNAs:
Proteins are produced in the body through a complex, two-step process.
First, during transcription, a DNA sequence is copied into mRNA inside the cell’s nucleus. This mRNA travels through the cell fluid and attaches to a ribosome.
In the Second step, called translation, transfer RNA (tRNA) brings the correct amino acids to the ribosome. These amino acids are linked together in the specific sequence dictated by the mRNA to create the protein.
MicroRNA steps in during this process, binding to and silencing mRNA at just the right time, in what is known as post-transcriptional gene regulation.
Discovery of MicroRNAs: Victor Ambros’ lab made the initial discovery of miRNAs in 1993 while studying a tiny roundworm, C. elegans, and its gene lin-14. Simultaneously, Gary Ruvkun identified the first mRNA target gene. Their pioneering work revealed a new mechanism for regulating gene expression after transcription.
Production and Lifecycle of MicroRNA
The production of miRNA is somewhat similar to early protein synthesis steps:
- Step 1: When a microRNA gene is activated, the DNA strand opens and is transcribed into RNA, resulting in an initial transcript called primary miRNA (pri-miRNA).
- Step 2: In the nucleus, pri-miRNA is processed into a double-stranded precursor miRNA (pre-miRNA).
- Step 3: Pre-miRNA is then transported to the cytoplasm, where it is further processed into mature miRNA (about 22 nucleotides long).
- Final Step: The mature miRNA binds to the RNA interference silencing complex (RISC), allowing it to target specific mRNAs and either block their translation or trigger their destruction.
This process is essential for controlling how and when proteins are produced within cells, making miRNAs a key component in gene regulation and disease management.
Significance of MicroRNAs
MicroRNAs play a significant role in numerous biological processes, including cell proliferation, differentiation, programmed cell death (apoptosis), and the immune response.
- Biological Regulation: They regulate cholesterol metabolism and are involved in conditions like cardiomyopathies and stroke.
- Pregnancy: miRNAs are essential in pregnancy development, contributing to steps such as embryo implantation and maternal-fetal immune tolerance.
- Disease Implications: Changes in miRNA expression can lead to altered gene expression, contributing to various disorders. For instance, abnormal miRNA expression is linked to human cancers, and mutations in miRNA-related genes are associated with congenital hearing loss and skeletal disorders.
Applications: A single miRNA can regulate the expression of multiple genes, while a single gene may also be controlled by different miRNAs. This fine-tuning of gene expression is crucial for cellular diversity despite identical genetic information. Understanding these mechanisms is a vital step toward further research.
How do miRNAs Control Gene Expression?
MicroRNAs control gene expression by binding to mRNAs in the cell’s cytoplasm. Instead of being translated into proteins immediately, the targeted mRNA is either degraded or stored for later translation.
- Underexpression and Overexpression: If a specific miRNA is underexpressed, the protein it regulates may be overproduced, leading to imbalances within the cell.
2024 Nobel Prize in Physiology or Medicine
Why Were the Scientists Honored?
Victor Ambros and Gary Ruvkun received the Nobel Prize for uncovering a key principle governing how gene activity is regulated. This discovery has been monumental in understanding how each cell selects the tools it needs to perform specific tasks.
Their work on microRNAs provided an entirely new perspective on the inner workings of complex organisms like humans.
Understanding the Role of mRNA:
Genetic information is stored in the DNA of each cell’s nucleus. This data is transcribed into mRNA, which then carries the instructions for making proteins.
Each type of tissue in the body produces specific proteins to carry out its function—whether it’s helping muscles contract or allowing nerves to send signals. This delicate process of gene regulation ensures that the right genes are activated or silenced at the right time. When gene regulation malfunctions, it can lead to serious illnesses such as cancer, diabetes, and autoimmune disorders.
The Impact of microRNA:
MicroRNAs play a crucial role in this regulatory process. A single miRNA can regulate the expression of multiple genes, while one gene might also be controlled by various microRNAs.
This ability to fine-tune gene expression is what allows cells to perform their specialized functions, even though they all contain the same genetic information.
The discovery of microRNAs has opened new avenues for understanding diseases and exploring potential treatments, solidifying its importance in the medical and scientific community.
About the Nobel Prize:
The Nobel Prize is a prestigious set of five international awards given annually in the fields of Physics, Chemistry, Physiology or Medicine, Literature, and Peace.
- Origins: Established by the will of Alfred Nobel, the inventor of dynamite, the first prizes were awarded in 1901, marking the fifth anniversary of Nobel’s death.
- Expansion: In 1968, a sixth category, the Sveriges Riksbank Prize in Economic Sciences, was added, though it is not officially a Nobel Prize.
- Location: Most prizes are awarded in Stockholm, Sweden, with the Peace Prize being awarded in Oslo, Norway.
- Eligibility: Nobel Prizes are typically awarded to individuals, with the Peace Prize being the only one that can also be conferred upon institutions. No more than three individuals may share a prize.
Notable Medicine Laureates:
- James D. Watson, known for his groundbreaking work on DNA and genetics, is a previous Nobel laureate.
- The 2023 Nobel Prize in Medicine was awarded to Katalin Karikó and Drew Weissman for their pioneering research on messenger RNA (mRNA).
Nobel Prize and India:
- In 1913, Rabindranath Tagore became the first non-European and Indian to win the Nobel Prize, receiving it in Literature.
- Sir C.V. Raman became India’s first Nobel laureate in Physics in 1930, recognized for his discovery of the Raman Effect and his work on light scattering.
Victor Ambros and Gary Ruvkun:
- Both Ambros and Ruvkun are American biologists. Ambros is part of the Programme in Molecular Medicine at the University of Massachusetts, while Ruvkun is a professor of genetics at Harvard Medical School. Ruvkun also conducts research on RNA mechanisms at Massachusetts General Hospital.
- Their groundbreaking research uncovered a new class of small RNA molecules essential for regulating gene activity. This discovery was made while studying the roundworm Caenorhabditis elegans.
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