Medicine & USMLE

Small Interfering RNA (siRNA)

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RNA
  1. Messenger RNA (mRNA)
  2. Ribosomal RNA (rRNA)
  3. Transfer RNA (tRNA)
  4. Small Nuclear RNA (snRNA)
  5. MicroRNA (miRNA)
  6. Small Interfering RNA (siRNA)

Summary

Small interfering RNA, or siRNA, is a class of non-coding, double-stranded RNA that plays a role in regulation of gene expression through silencing of complementary mRNA via target degradation. Target degradation occurs through siRNA binding to target mRNA and causing it to be cleaved into fragments that are then further broken down. This prevents the mRNA from ever binding to ribosomes and thereby blocks translation. Importantly, target degradation requires perfect complementarity between the siRNA strand and the target mRNA strand.

Key Points

  • Small Interfering RNA (siRNA)
    • Naming
      • Small RNA molecules that actively interfere with the translation of proteins
        • Each contain only ~21-23 nucleotides
    • Characteristics
      • Class of non-coding RNA
        • Does not code for proteins
        • Also known as functional RNA
      • Double-stranded RNA (dsRNA)
      • Found in eukaryotes
        • Not known to be found in prokaryotes
    • Function
      • Plays a role in post-transcriptional regulation of gene expression
      • Silencing of complementary mRNA
        • Target degradation occurs by associating with an RNA-induced silencing complex (RISC) and subsequent cleavage of the target mRNA
          • siRNA is cleaved into two strands
            • A guide strand is loaded into RISC
            • A passenger strand is degraded by endonucleases
          • Guide siRNA strand scans for and directs RISC to complementary sequences on target mRNA and binds to it
            • Binding causes RISC to cleave target mRNA into fragments
          • mRNA fragments are then degraded by exonucleases
        • Requires perfect complementarity
          • Binding and inhibition can ONLY occur with perfect complementarity to the target mRNA
    • Synthesis
      • dsRNA (either transcribed from cellular genes or infecting pathogens, or artificially introduced into the cells) is processed by a specialized ribonuclease enzyme named Dicer in the cytoplasm into a smaller dsRNA molecule, known as siRNA