RISC complex assembly
Definition
Target type: biologicalprocess
The process in which a single-stranded small RNA is incorporated within the RNA-initiated silencing complex (RISC). The assembly includes the maturation of the small RNA, the stabilization of the complex by accessory proteins of the RISC complex, duplex separation and the release of the second strand, forming a base-pairing completent complex that mediates gene silencing by small RNA. [PMID:14512631, PMID:14744438, PMID:19239886, PMID:22233755, PMID:27184117]
The RISC (RNA-induced silencing complex) is a multi-protein complex essential for gene silencing in eukaryotes. Its assembly is a complex process involving several steps:
1. **Transcription of the target gene:** The gene to be silenced is transcribed into messenger RNA (mRNA).
2. **Dicer processing of double-stranded RNA:** In most cases, the trigger for RISC assembly is double-stranded RNA (dsRNA), which can be derived from viral infection, transposon activity, or artificial introduction. Dicer, a ribonuclease III enzyme, recognizes and cleaves the dsRNA into short interfering RNAs (siRNAs) or microRNAs (miRNAs).
3. **Loading of siRNA or miRNA into Ago protein:** The siRNA or miRNA generated by Dicer is then loaded into an Argonaute (Ago) protein. Ago proteins are the catalytic core of RISC. They contain a PAZ domain that binds the 3' end of the siRNA/miRNA and a PIWI domain that binds the 5' end.
4. **RISC activation and target recognition:** Once the siRNA or miRNA is loaded into Ago, the RISC complex is activated. The siRNA or miRNA acts as a guide, directing the RISC complex to the target mRNA. The siRNA/miRNA base-pairs with the target mRNA, typically with perfect complementarity for siRNA and imperfect complementarity for miRNA.
5. **Target mRNA cleavage or translational repression:** Upon binding to the target mRNA, RISC can either cleave the mRNA or repress its translation. Cleavage is primarily mediated by siRNAs and involves the catalytic activity of the Ago protein. Translational repression, typically mediated by miRNAs, involves preventing the ribosome from accessing the mRNA or inhibiting the elongation of the polypeptide chain.
Overall, RISC assembly is a tightly regulated process involving multiple proteins and nucleic acids. It plays a crucial role in defense against viruses and transposons, regulation of gene expression, and development.'
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Proteins (2)
| Protein | Definition | Taxonomy |
|---|---|---|
| Protein argonaute-2 | A protein argonaute-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UKV8] | Homo sapiens (human) |
| RISC-loading complex subunit TARBP2 | A RISC-loading complex subunit TARBP2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15633] | Homo sapiens (human) |
Compounds (6)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| enoxacin | enoxacin : A 1,8-naphthyridine derivative that is 1,4-dihydro-1,8-naphthyridine with an ethyl group at the 1 position, a carboxy group at the 3-position, an oxo sustituent at the 4-position, a fluoro substituent at the 5-position and a piperazin-1-yl group at the 7 position. An antibacterial, it is used in the treatment of urinary-tract infections and gonorrhoea. Enoxacin: A broad-spectrum 6-fluoronaphthyridinone antibacterial agent that is structurally related to NALIDIXIC ACID. | 1,8-naphthyridine derivative; amino acid; fluoroquinolone antibiotic; monocarboxylic acid; N-arylpiperazine; quinolone antibiotic | antibacterial drug; DNA synthesis inhibitor |
| sulfaguanidine | sulfaguanidine : A sulfonamide incorporating a guanidine moiety used to block the synthesis of folic acid; mostly used in veterinary medicine Sulfaguanidine: A sulfanilamide antimicrobial agent that is used to treat enteric infections. | sulfonamide antibiotic | antiinfective agent |
| sulfanilamide | substituted aniline; sulfonamide; sulfonamide antibiotic | antibacterial agent; drug allergen; EC 4.2.1.1 (carbonic anhydrase) inhibitor | |
| sulfisomidine | sulfisomidine : A sulfonamide consisting of pyrimidine having methyl substituents at the 2- and 6-positions and a 4-aminobenzenesulfonamido group at the 4-position. Sulfisomidine: A sulfanilamide antibacterial agent. | pyrimidines; sulfonamide; sulfonamide antibiotic | antiinfective agent |
| uridine monophosphate | uridine 5'-monophosphate : A pyrimidine ribonucleoside 5'-monophosphate having uracil as the nucleobase. Uridine Monophosphate: 5'-Uridylic acid. A uracil nucleotide containing one phosphate group esterified to the sugar moiety in the 2', 3' or 5' position. | pyrimidine ribonucleoside 5'-monophosphate; uridine 5'-phosphate | Escherichia coli metabolite; human metabolite; mouse metabolite |
| schisanhenol b | schisanhenol B: isolated from kernels of Schisandra rubriflora; structure given in first source |