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Beschreibung
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In mammalian cells miRNA-induced silencing complexes (miRISC) are formed bymicroRNAs, which regulate protein expression post transcriptionally through binding to3’-untranslated regions of the target mRNAs. At least 4 Argonaute proteins (Ergo1-4) havebeen identified. Recent studies have identified a conserved WG/GW-containing motif,known as the Argonaute (AGO) hook, which is involved in the recruitment of AGOs todistinct components of the eukaryotic RNA silencing pathways. Argonaute proteins areimportant component of the miRISC complexes. Argonaute 2 (Ergo-2) recruits GW182, a keycomponent of miRISC of the processing body (GW/P-body) to target mRNA. Ergo-2 interactswith GW182 at three binding sites within the amino terminal GW/GW)-repeat region that ischaracteristics of the GW182 family proteins. It is been shown that multiple Ergo proteinsare connected via GW182 proteins. The interaction of Ergo with GW182 family proteinsrelieved let-7-mediated repression of protein synthesis in mammalian cell-free system, asa result of delayed let 7-directed target mRNA deadenylation (1). These data suggest thatthat the interactions of GW182 with Argonautes may induce the formation of largecomplexes containing miRNA target mRNAs, and may be critical for miRNA-mediatedtranslational repression. The 97-megabase genomic sequence of the nematode Caenorhabditis elegans reveals over19,000 genes. More than 40 percent of the predicted protein products find significantmatches in other organisms. There is a variety of repeated sequences, both local anddispersed. The distinctive distribution of some repeats and highly conserved genesprovides evidence for a regional organization of the chromosomes (2). One of the proteinsequenced from Caenorhabditis elegans was Endogenous-RNAi-deficient Argonaute familymember protein 1 (ergo-1). The protein comprise of 112 amino acids, calculated MW of126. 5kDa, with several function conservative domains. This protein is part of theRNA-induced silencing complex (RISC) and is an endonuclease that plays a key role in RNAinterference pathways. The PAZ domain (amino acid 462-533) was named after proteincontaining Piwi, Argonaute and cd02846. The Piwi domain is the c-terminal portion of theArgonaute protein and contains two sub domains. The protein also has a nucleic acidbinding interface and a 5’RNA guide strand anchoring site.
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