ZOOHCC - 501: Molecular Biology (Theory)
Unit 3: Transcription and Regulatory RNAs
RNA interference
RNA interference (RNAi) is the regulation of gene expression by small RNA molecules, such as small interfering RNAs (siRNAs) and microRNAs (miRNAs), that target mRNA molecules for degradation or translation and inhibit proteins. It is a biological process that
RNAi plays an important role in many cellular processes, including development, differentiation, and defense against viruses and other pathogens. It also has important applications in biomedical research, such as gene therapy development and the study of gene function.
The RNAi pathway begins with the synthesis of double-stranded RNA molecules that are processed into smaller RNA molecules by an enzyme called Dicer. These small RNA molecules then associate with a protein complex called the RNA-induced silencing complex (RISC) and direct it to the target mRNA molecule based on complementary base-pairing. When a small RNA molecule and its associated RISC complex bind to a target mRNA, the mRNA molecule is either cleaved by the RISC complex, preventing translation of the mRNA into protein, or destabilized and degraded.
RNAi has become an important tool for studying gene function, allowing researchers to selectively turn off specific genes and observe their effects on cellular processes or whole organisms. It also has potential therapeutic applications, such as treating genetic diseases and viral infections.
miRna
miRNA, short for microRNA, is a class of small RNA molecules involved in regulating gene expression. These are short (approximately 20–22 nucleotides long) RNA molecules that play important roles in many biological processes, including development, differentiation, and disease.
miRNAs function by binding to complementary sequences in target messenger RNA (mRNA) molecules, resulting in mRNA degradation and inhibition of protein translation. Because miRNAs can regulate the expression of multiple genes simultaneously, they are important in regulating complex cellular processes.
Aberrant expression of miRNAs is associated with many diseases, including cancer, cardiovascular disease, and neurodegenerative disease. Understanding the role of miRNAs in health and disease is an active research area, and miRNAs are being explored as potential therapeutic targets for various diseases.
How It Works
MicroRNAs are the name for a family of molecules that help control the types and amounts of proteins that cells produce. That is, cells use microRNAs to control gene expression. MicroRNA molecules are found intracellularly and in the bloodstream. (Note: microRNA is abbreviated as "miRNA", but "microRNA" is used here.)
Gene expression refers to whether a particular gene is producing too much, too little, or normal amount of that protein at a particular time.
To understand the workings of gene expression and microRNAs, it helps to understand how cells use the DNA of genes to make proteins. This is done through a four-step process called protein synthesis.
Controls gene expression
MicroRNAs regulate gene expression primarily by binding to messenger RNAs (mRNAs) in the cytoplasm of cells. Instead of being rapidly translated into protein, the tagged mRNA is either destroyed and its components recycled or stored for later translation.
Therefore, if the level of a particular microRNA is underexpressed (abnormally low levels in cells), it is possible that the proteins that normally regulate it are overexpressed (abnormally low levels in cells). higher). When a microRNA is overexpressed (its levels are abnormally high), its proteins are underexpressed (its levels are abnormally low).
siRNA
siRNA stands for "small interfering RNA". It is a class of small RNA molecules that play an important role in RNA interference (RNAi), a biological process that regulates gene expression.
siRNAs are double-stranded RNA molecules, usually 21-23 nucleotides in length. They are involved in posttranscriptional gene silencing. In other words, they target specific messenger RNA (mRNA) molecules for degradation and repression of gene expression.
The siRNA pathway begins with the introduction of double-stranded RNA molecules into the cell. An enzyme called Dicer then cleaves the double-stranded RNA into smaller pieces, such as siRNA. These siRNAs then associate with a protein complex called the RNA-induced silencing complex (RISC) and direct it to the target mRNA molecule. The siRNA-RISC complex then cleaves the target mRNA, causing its degradation and subsequent suppression of gene expression.
The ability of siRNAs to target specific genes makes them important tools in biomedical research, with potential applications in gene therapy and treatment of diseases such as cancer and viral infections.
Role os siRNA
Short (or small) interfering RNAs (siRNAs) are similar in size and function to microRNAs because they target and denature gene transcripts through processes mediated by the RNA-induced silencing complex (RISC). miRNAs have the ability to regulate tens or hundreds of gene targets through imperfect base-pairing, whereas siRNAs bind specifically to single gene sites (Kim, 2005; Lam et al. ., 2015). This property has spurred the development of molecular tools and therapeutics using siRNAs, as mechanisms have been shown to promote specific RNA interference (RNAi) in mammalian cells.
Origin of Short-Interfering RNAs
Because siRNAs are the most widely distributed among the known eukaryotic small RNAs a siRNA-like system may be the ancestral type of RNA-based regulation in eukaryotes (Shabalina and Koonin, 2008). This hypothesis is supported by shared features between siRNAs and miRNAs as well as between siRNAs and some other features with piRNAs. For example, both siRNAs and miRNAs associate with Dicer and Argonaute, whereas some siRNAs and piRNAs share functions to suppress transposons as mentioned in later sections.
To understand the diversification of siRNAs after origination, let us consider exo- and endo-siRNAs separately. Ancestral siRNAs are likely to have been exo-siRNAs derived from viruses and other parasitic RNAs, and that the first siRNA machinery in early eukaryotes was established to fight against these `genomic predators.` Endo-siRNAs later came into existence as the functions of siRNAs began to diversify. Endo-siRNAs that are generated from transposons and heterochromatic sequences are apparently involved in the silencing of transposons and repetitive elements, whereas those from pseudogenes likely regulate their functional homologs. In some cases, endo-siRNAs are also made from mRNA. A subset of these endo-siRNAs can form long hairpins and thus may be the ancestral state of miRNAs.
