Argonaute MID domain takes centre stage

Faehnle, C.R.; Joshua‐Tor, Leemor

doi:10.1038/embor.2010.110

Cited by 19 publications

(14 citation statements)

References 9 publications

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“…Until very recently, all structural work on AGO proteins has focused on either isolated fragments of eukaryotic AGO proteins or on full-length proteins from thermophilic bacteria or archaea (Faehnle and Joshua-Tor, 2010). The thermophile AGO proteins have no known endogenous function and have fundamentally different biochemical properties because they use guide DNA strands.…”

Section: Eukaryotic Ago Structures Eukaryotic Ago Structures As Modelmentioning

confidence: 99%

Lessons on RNA Silencing Mechanisms in Plants from Eukaryotic Argonaute Structures

2013

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RNA silencing refers to a collection of gene regulatory mechanisms that use small RNAs for sequence specific repression. These mechanisms rely on ARGONAUTE (AGO) proteins that directly bind small RNAs and thereby constitute the central component of the RNA-induced silencing complex (RISC). AGO protein function has been probed extensively by mutational analyses, particularly in plants where large allelic series of several AGO proteins have been isolated. Structures of entire human and yeast AGO proteins have only very recently been obtained, and they allow more precise analyses of functional consequences of mutations obtained by forward genetics. To a large extent, these analyses support current models of regions of particular functional importance of AGO proteins. Interestingly, they also identify previously unrecognized parts of AGO proteins with profound structural and functional importance and provide the first hints at structural elements that have important functions specific to individual AGO family members. A particularly important outcome of the analysis concerns the evidence for existence of Gly-Trp (GW) repeat interactors of AGO proteins acting in the plant microRNA pathway. The parallel analysis of AGO structures and plant AGO mutations also suggests that such interactions with GW proteins may be a determinant of whether an endonucleolytically competent RISC is formed.

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Section: Eukaryotic Ago Structures Eukaryotic Ago Structures As Modelmentioning

confidence: 99%

Lessons on RNA Silencing Mechanisms in Plants from Eukaryotic Argonaute Structures

2013

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“…Such a nucleotide-specific loop has also been observed in the recently solved crystal structure of full-length eukaryotic AGOs (Fig. However, a similar nucleotide-specific loop is not observed in the crystal structure of Neurospora crassa AGO (QDE-2) MID domain (Boland et al, 2010;Faehnle & Joshua-Tor, 2010), which raises the question whether the nucleotide-specific loop is a universal structural feature for small RNA sorting by eukaryotic AGOs. However, a similar nucleotide-specific loop is not observed in the crystal structure of Neurospora crassa AGO (QDE-2) MID domain (Boland et al, 2010;Faehnle & Joshua-Tor, 2010), which raises the question whether the nucleotide-specific loop is a universal structural feature for small RNA sorting by eukaryotic AGOs.…”

Section: (3) Ago Proteins (Agos)mentioning

confidence: 78%

Structural insights into the arms race between host and virus along RNA silencing pathways in Arabidopsis thaliana

2013

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RNA silencing refers to a conserved sequence-specific gene-regulation mechanism mediated by small RNA molecules. In plants, microRNA (miRNA) and small interfering RNA (siRNA) represent two major types of small RNA molecules which play pivotal roles in plant developmental control and antiviral defences. To escape these plant defences, plant viruses have encoded a vast array of viral suppressors of RNA silencing (VSRs) to attack the host antiviral silencing pathway by interfering with small RNA processing, RNA-induced silencing complex (RISC) assembly, viral mRNA cleavage etc. Transgenic plants expressing distinct VSRs often show developmental aberrations that resemble the phenotype of miRNA-deficient mutants, implying a potential intrinsic link between VSRs and the miRNA pathway (at least in Arabidopsis thaliana) even though their pathogenic mechanisms remain largely unknown. In this review, we summarise our current structural understandings of the arms race between the host and virus along the RNA silencing pathway in A. thaliana by focusing on several important ribonucleoprotein (RNP) structures involved in RNA silencing and unique structural features adopted by VSRs.

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“…2D–F). In Nc_QDE2, sulfate II is 6.3 Å from sulfate I, shares coordination with Lys599 and Lys638, and is further coordinated by Thr610 [Faehnle and Joshua‐Tor, 2010]. And sulfate II is bound in the side of the MID domain opposite from where the guide RNA extends from the 5′‐nucleotide binding site, so sulfate II cannot compete with sulfate I [Faehnle and Joshua‐Tor, 2010].…”

Section: Resultsmentioning

confidence: 99%

Structural evolution and functional diversification analyses of argonaute protein

Wei

Chen

et al. 2012

J of Cellular Biochemistry

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Argonaute (AGO) proteins are highly specialized small-RNA-binding modules and small RNAs are anchored to their specific binding pockets guiding AGO proteins to target mRNA molecules for silencing or destruction. The 135 full-length AGO protein sequences derived from 36 species covering prokaryote, archaea, and eukaryote are chosen for structural and functional analyses. The results show that bacteria and archaeal AGO proteins are clustered in the same clade and there exist multiple AGO proteins in most eukaryotic species, demonstrating that the increase of AGO gene copy number and horizontal gene transfer (HGT) have been the main evolutionary driving forces for adaptability and biodiversity. And the emergence of PAZ domain in AGO proteins is the unique evolutionary event. The analysis of middle domain (MID)-nucleotide contaction shows that either the position of sulfate I bond in Nc_QDE2 or the site of phosphate I bond in Hs_AGO2 represents the 5'-nucleotide binding site of miRNA. Also, H334, T335, and Y336 of Hs_AGO1 can form hydrogen bonds with 3'-overhanging ends of miRNAs and the same situation exists in Hs_AGO2, Hs_AGO3, Hs_AGO4, Dm_AGO1, and Ce_Alg1. Some PIWI domains containing conserved DDH motif have no slicer activity, and post-translational modifications may be associated with the endonucleolytic activities of AGOs. With the numbers of AGO genes increasing and fewer crystal structures available, the evolutionary and functional analyses of AGO proteins can help clarify the molecular mechanism of function diversification in response to environmental changes, and solve major issues including host defense mechanism against virus infection and molecular basis of disease.

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Argonaute MID domain takes centre stage

Abstract: Two recent papers, one in EMBO reports and one in Nature give us the first eukaryotic structures of Argonaute MID domains; providing a structural basis for the 5′‐nucleotide recognition of the guide strand and a possible explanation for the allosteric regulation of RNA binding.

Cited by 19 publications

References 9 publications

Lessons on RNA Silencing Mechanisms in Plants from Eukaryotic Argonaute Structures

Lessons on RNA Silencing Mechanisms in Plants from Eukaryotic Argonaute Structures

Structural insights into the arms race between host and virus along RNA silencing pathways in Arabidopsis thaliana

Structural evolution and functional diversification analyses of argonaute protein

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