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.