module: dmel_risc_loading_complexes
title: RISC-loading complexes and miRISC in Drosophila melanogaster
label: RISC loading complexes
module_type: PROTEIN_COMPLEX
description: >-
  Small RNA duplexes produced by Dicer are loaded into Argonaute proteins by
  RISC-loading complexes. In Drosophila the miRNA pathway uses Dicer-1 with the
  dsRNA-binding partner Loquacious (Loqs-PB) and loads miRNAs mainly into AGO1,
  whereas the siRNA pathway uses Dicer-2 with R2D2, which senses duplex
  asymmetry and loads siRNAs into AGO2. FlyBase also defines an alternative
  siRNA loading complex in which Loqs (Loqs-PD isoform) partners Dicer-2 with
  AGO2. Mature miRNA-loaded AGO1 associates with the GW182 protein Gawky to form
  the miRNA-induced silencing complex (miRISC), which represses translation and
  promotes deadenylation and decay of target mRNAs.
summary: >-
  Dicer-dsRBD protein-Argonaute loading complexes for miRNAs and siRNAs, and the
  AGO1-Gawky miRISC.
concepts:
  - {id: GO:0070578, label: RISC-loading complex}
  - {id: GO:0016442, label: RISC complex}
parts:
  - id: mirna_loading
    label: miRNA RISC-loading complex
    role: miRNA duplex loading into AGO1
    group: miRLC
    complex_term: {id: GO:0070578, label: RISC-loading complex}
    unit_functions:
      Dcr-1: {id: GO:0004525, label: ribonuclease III activity}
    processes:
      - {id: GO:0070922, label: RISC complex assembly}
  - id: sirna_loading
    label: siRNA RISC-loading complexes
    role: siRNA duplex loading into AGO2
    variant_sets:
      - id: sirna_loading_variants
        label: R2D2 or Loqs as Dicer-2 partner
        selection: ONE_OR_MORE
        variants:
          - id: sirlc
            label: Dcr-2-R2D2-AGO2 siRNA RISC-loading complex
            group: siRLC
            complex_term: {id: GO:0070578, label: RISC-loading complex}
            unit_functions:
              Dcr-2: {id: GO:0004525, label: ribonuclease III activity}
            processes:
              - {id: GO:0070922, label: RISC complex assembly}
          - id: arlc
            label: Alternative Dcr-2-Loqs-AGO2 siRNA RISC-loading complex
            group: aRLC
            complex_term: {id: GO:0070578, label: RISC-loading complex}
            unit_functions:
              Dcr-2: {id: GO:0004525, label: ribonuclease III activity}
            processes:
              - {id: GO:0070922, label: RISC complex assembly}
  - id: mirisc
    label: miRNA-induced silencing complex
    role: miRNA-guided repression of target mRNAs
    group: miRISC
    complex_term: {id: GO:0016442, label: RISC complex}
    processes:
      - {id: GO:0035195, label: miRNA-mediated post-transcriptional gene silencing}
connections:
  - source: mirna_loading
    target: mirisc
    connection_type: PRECEDES
    description: miRNA-loaded AGO1 leaves the loading complex and binds Gawky to form miRISC.
notes: >-
  Parts follow FlyBase groups miRLC, siRLC, aRLC and miRISC. The Loqs isoform
  specificity (Loqs-PB in the miRNA loading complex, Loqs-PD in the
  alternative siRNA loading complex) cannot be expressed at gene level here.
  Ribonuclease III activity is given to the Dicers only. Downstream effectors
  of miRISC (CCR4-NOT, decapping) and the piRNA pathway are outside this
  module.