The microRNA Machinery

Adv Exp Med Biol. 2015:887:15-30. doi: 10.1007/978-3-319-22380-3_2.

Abstract

MicroRNAs (miRNAs) are short (~22 nucleotides) single-stranded RNA molecules that primarily function to negatively regulate gene expression at the post-transcriptional level. miRNAs have thus been implicated in the regulation of a wide variety of normal cell functions and pathophysiological conditions. The miRNA machinery consists of a series of protein complexes which act to: (1) cleave the precursor-miRNA hairpin from its primary transcript (i.e. DROSHA and DGCR8); (2) traffic the miRNA hairpin between nucleus and cytoplasm (i.e. XPO5); (3) remove the loop sequence of the hairpin by a second nucleolytic cleavage reaction (i.e. DICER1); (4) facilitate loading of the mature miRNA sequence into an Argonaute protein (typically AGO2) as part of the RNA-Induced Silencing Complex (RISC); (5) guide the loaded RISC complex to complementary, or semi-complementary, target transcripts and (6) facilitate gene silencing via one of several possible mechanisms.

Keywords: AGO2; Argonaute; DGCR8; DICER1; Dicer; Drosha; Exportin-5; XPO5; microRNA.

MeSH terms

  • Animals
  • Argonaute Proteins / chemistry
  • Argonaute Proteins / metabolism*
  • Carboxypeptidases / chemistry
  • Carboxypeptidases / metabolism*
  • DEAD-box RNA Helicases / chemistry
  • DEAD-box RNA Helicases / metabolism*
  • Gene Expression Regulation
  • Humans
  • Karyopherins / chemistry
  • Karyopherins / metabolism*
  • MicroRNAs / chemistry
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Models, Molecular
  • Nucleic Acid Conformation
  • Protein Conformation
  • RNA Cleavage
  • RNA Transport
  • Ribonuclease III / chemistry
  • Ribonuclease III / metabolism*

Substances

  • AGO2 protein, human
  • Argonaute Proteins
  • Karyopherins
  • MicroRNAs
  • XPO5 protein, human
  • DICER1 protein, human
  • Ribonuclease III
  • Carboxypeptidases
  • SCPEP1 protein, human
  • DEAD-box RNA Helicases