Argonaut proteins
![](https://upload.wikimedia.org/wikipedia/commons/thumb/0/02/1u04-argonaute.png/330px-1u04-argonaute.png)
Argonaut proteins (AGO) are a family of proteins whose representatives are evolutionarily strongly conserved. They occur in almost all organisms, where they play an important role in the activation and regulation of genes. Representatives of the AGO family are involved in post-transcriptional gene silencing (PTGS), which includes RNA interference (RNAi) and mRNA degradation caused by microRNA .
construction
Argonaut proteins are predominantly basic proteins and consist of two functional domains, PAZ and PIWI; Total mass about 100 kDa . The PAZ domain consists of 130 amino acids and can also be found in the Dicer protein . It binds the targeting si / miRNA and possibly also serves as a protein-protein interaction domain for the endonuclease Dicer. The C-terminal PIWI domain has the Mg 2+ -dependent endonuclease activity against the substrate mRNA to be cut.
Classification
Argonaut proteins are divided into three classes on the basis of matches in the protein sequence :
- Argonaute-like protein → is similar to the Arabidopsis thaliana protein AGO1
- PIWI-like protein → strong relationship to PIWI protein from Drosophila melanogaster
- group-3-Argonautes → recently discovered group of Argonaut proteins in Caenorhabditis elegans
Argonaut proteins are part of the so-called RNA-induced silencing complex ( RISC ), which plays a central role in RNA interference. Ago2 binds the small interfering RNA (siRNA) or micro-RNA (miRNA) and first cuts their non-targeting complementary strand, so that a single-stranded siRNA / miRNA is created. After successful binding, the argonaut protein cuts the substrate mRNA via an endonuclease activity. Otherwise the translation of the substrate mRNA is only blocked, for which no endonuclease activity is required. Before the siRNA can bind, argonaut proteins form complexes with DICER; in a maximum description, DICER, TRBP, Ago2 and other proteins are present as protein complexes of the RISC. After cutting the starting dsRNA into siRNA or pre-miRNA, DICER dissociates from the now active RISC.
Depending on the organism, the genome encodes 5 (e.g. fruit flies ), 8 (e.g. humans) or even up to 27 (e.g. Caenorhabditis elegans ) argonaut proteins. However, there are also organisms such as B. the parasite Trypanosoma cruzi , which in the course of evolution have laid down their entire RNAi machinery and only have catalytically inactive AGO proteins.
literature
- TA Rand u. a .: Biochemical Identification of Argonaute 2 as the sole protein required for RNA induced silencing complex activity . PNAS 2004; 101: 14385, PMID 15452342
- RI Gregory et al. a .: Human RISC couples microRNA biogenesis and posttranscriptional gene silencing . Cell 2005; 123: 631, PMID 16271387
- E. Maniataki, Z. Morelatos: A human, ATP-independent, RISC assembly machine fueled by pre-miRNA . Genes Dev 2005; 19: 2979, PMID 16357216
- G. Meister, Thomas Tuschl u. a .: Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs . Mol Cell 2004; 15: 185, PMID 15260970
- TA Rand, X. Wang et al. a .: Argonaute2 cleaves the anti-guide strand of siRNA during RISC activation . Cell 2005; 123: 621, PMID 16271385
- MA Carmell, Z. Xuan, MQ Zhang, GJ Hannon: The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis . Genes Dev. 2002 Nov 1; 16 (21): 2733-42. Review. PMID 12414724
- K. Jaronczyk, JB Carmichael, TC Hobman: Exploring the functions of RNA interference pathway proteins: some functions are more RISCy than others? . Biochem. J. (2005) 387 (561-571) ( full text )
- Gyorgy Hutvagner, Martin J. Simard: Argonaute proteins: key players in RNA silencing . Nature Reviews Molecular Cell Biology 9, 22-32 (January 2008)
Web links
- The microRNA world: small is mighty (PDF; 331 kB)
- David Goodsell: Molecule of the Month: Small Interfering RNA (siRNA)