MICRORNAS IN THE LIVER HELP REGULATE THE FEED-FAST CYCLE
21, Apr 2019
Prelims level : Scientific Exploration Mains level : GS-III Science and Technology
Why in News:
- Researchers from Tata Institute of Fundamental Research (TIFR), Mumbai, have succeeded in identifying the mechanism that drives the feed-fast transition in the liver. They find that the oscillation in the levels of certain microRNAs in the liver drives this transition, and they inhibit the translation of the fasting responsive genes.
- The feed-fast cycle is an important aspect of our body metabolism.
- The four stages are fed state, post-absorptive state, fasting state, starvation state. Humans only experience the third stage and do not enter the fasting stage.
- Different organs in our body work to metabolise the food we consume, and they behave differently during each stage.The liver is a central organ in maintaining glucose and fat metabolism both under fed and fasted conditions. During a fasting state, liver produces glucose in a process which is critical for maintaining circulating glucose levels.
- An abnormality in either of these processes can lead to diabetes, obesity or other liver diseases. Aberrant molecular mechanisms that affect glucose and fat metabolism in the liver are the primary causes of several metabolic diseases and even ageing. Many of these occur due to aberrant gene expression and metabolic stress.
- fasting lasts from a few hours to days, feeding is a rapid process that takes from a few minutes to an hour. Therefore, when going from fasting to feeding, the liver functions must switch rapidly. This entails stopping the mRNA translation of fasting-induced genes in a fed state.
- Research is done by profiling microRNAs in the liver of mice models in a fed state in which identified that these fed microRNAs could control the expression of fasting-induced genes, thus controlling liver metabolism, mitochondrial functions and cellular respiration.
- By injecting molecular sponges that scavenged the microRNAs in the liver, it would reduce the level of fed microRNAs.
- The gene expression and metabolic pathways in the liver results in elevated glucose production and higher circulating blood glucose levels in the mice. The study is significant in having discovered changes in microRNA levels which constitutes an anticipatory mechanism and whose abrogation leads to a diabetic like state. Most of the mechanisms are conserved between humans and mice. So identifying such fed microRNAs in humans can aid in developing therapeutic interventions for tackling lifestyle disorders and ageing- associated loss in physiological fitness.
- Ribonucleic acid (RNA), is quite similar to DNA. DNA molecules are typically long and double stranded, RNA molecules are much shorter and are typically single stranded.
- RNA molecules perform a variety of roles in the cell but are mainly involved in the process of protein synthesis (translation) and its regulation.
- RNA is typically single stranded and is made of ribonucleotides that are linked by phosphodiester bonds. A ribonucleotide in the RNA chain contains ribose (the pentose sugar), one of the four nitrogenous bases (A, U, G, and C), and a phosphate group.
- The subtle structural difference between the sugars gives DNA added stability, making DNA more suitable for storage of genetic information, whereas the relative instability of RNA makes it more suitable for its more short-term functions. The RNA-specific pyrimidine uracil forms a complementary base pair with adenine and is used instead of the thymine used in DNA. Even though RNA is single stranded, most types of RNA molecules show extensive intramolecular base pairing between complementary sequences within the RNA strand, creating a predictable three-dimensional structure essential for their function
Functions of RNA in Protein Synthesis
- Cells access the information stored in DNA by creating RNA to direct the synthesis of proteins through the process of translation.
- Proteins within a cell have many functions, including building cellular structures and serving as enzyme catalysts for cellular chemical reactions that give cells their specific characteristics. The three main types of RNA directly involved in protein synthesis are messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA).
- French scientists François Jacob and Jacques Monod hypothesized the existence of an intermediary between DNA and its protein products, which they called messenger RNA.
- The information from DNA is transmitted to the ribosome for protein synthesis using mRNA. If DNA serves as the complete library of cellular information, mRNA serves as a photocopy of specific information needed at a particular point in time that serves as the instructions to make a protein. The mRNA carries the message from the DNA, which controls all of the cellular activities in a cell. If a cell requires a certain protein to be synthesized, the gene for this product is “turned on” and the mRNA is synthesized through the process of transcription. The mRNA then interacts with ribosomes and other cellular machinery to direct the synthesis of the protein it encodes during the process of translation.
- mRNA is relatively unstable and short-lived in the cell, especially in prokaryotic cells, ensuring that proteins are only made when needed.
- rRNA and tRNA are stable types of RNA. In prokaryotes and eukaryotes, tRNA and rRNA are encoded in the DNA, then copied into long RNA molecules that are cut to release smaller fragments containing the individual mature RNA species. In eukaryotes, synthesis, cutting, and assembly of rRNA into ribosomes takes place in the nucleolus region of the nucleus, but these activities occur in the cytoplasm of prokaryotes. Neither of these types of RNA carries instructions to direct the synthesis of a polypeptide, but they play other important roles in protein synthesis.
- Ribosomes are composed of rRNA and protein. As its name suggests, rRNA is a major constituent of ribosomes, composing up to about 60% of the ribosome by mass and providing the location where the mRNA binds. The rRNA ensures the proper alignment of the mRNA, tRNA, and the ribosomes; the rRNA of the ribosome also has an enzymatic activity (Peptidyl transferase) and catalyzes the formation of the peptide bonds between two aligned amino acids during protein synthesis.
RNA as Hereditary Information
- Although RNA does not serve as the hereditary information in most cells, RNA does hold this function for many viruses that do not contain DNA. Thus, RNA clearly does have the additional capacity to serve as genetic information.
- Although RNA is typically single stranded within cells, there is significant diversity in viruses. Rhinoviruses, which cause the common cold, influenza viruses and the Ebola virus are single-stranded RNA viruses.
- Rotaviruses, which cause severe gastroenteritis in children and other immunocompromised individuals, are examples of double-stranded RNA viruses. Because double-stranded RNA is uncommon in eukaryotic cells, its presence serves as an indicator of viral infection