The Making of a Slicer: Activation of Human Argonaute-1

Faehnle, C.R.; Elkayam, Elad; Haase, Astrid D.; Hannon, Gregory J.; Joshua‐Tor, Leemor

doi:10.1016/j.celrep.2013.05.033

Cited by 128 publications

(207 citation statements)

References 38 publications

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“…Structures of human AGO1 bound to endogenous co-purified RNAs or loaded with let-7 miRNA are strikingly similar to the structures of AGO2 (Faehnle et al, 2013;Nakanishi et al, 2013). Evolutionary changes that rendered hAGO1 inactive included a mutation of a catalytic tetrad residue and mutations on a loop near the actives site (Faehnle et al, 2013;Nakanishi et al, 2013).…”

Section: Human Ago1 and Ago2 Structuresmentioning

confidence: 77%

“…The core of the structural reports is thus formed by six articles reporting crystal structures of human Argonaute proteins (Elkayam et al, 2012;Schirle and MacRae, 2012;Faehnle et al, 2013;Nakanishi et al, 2013;Schirle et al, 2014;Schirle et al, 2015). Four articles describe crystal structures of AGO2 (Elkayam et al, 2012;Schirle and MacRae, 2012;Schirle et al, 2014;Schirle et al, 2015), which is capable of cleaving cognate transcripts and two describe miRNA-pathway dedicated AGO1 (Faehnle et al, 2013;Nakanishi et al, 2013).…”

Section: Ago2 Structure and Functionmentioning

confidence: 99%

“…Evolutionary changes that rendered hAGO1 inactive included a mutation of a catalytic tetrad residue and mutations on a loop near the actives site (Faehnle et al, 2013;Nakanishi et al, 2013).…”

Section: Human Ago1 and Ago2 Structuresmentioning

confidence: 99%

See 2 more Smart Citations

Literature review of baseline information to support the risk assessment of RNAi‐based GM plants

Pačes

Nič²,

Novotný³

et al. 2017

EFS3

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This report is the outcome of an EFSA procurement aiming at investigating and summarising the state of knowledge on (I) the mode-of-action of dsRNA and miRNA pathways, (II) the potential for nontarget gene regulation by dsRNA-derived siRNAs or miRNAs, (III) the determination of siRNA pools in plant tissues and the importance of individual siRNAs for silencing. The report is based on a comprehensive and systematic literature search, starting with the identification and retrieval of~190,000 publications related to the research area and further filtered down with keywords to produce focused collections used for subsequent screening of titles and abstracts. The report is comprised of an (I) Introduction to the field of small RNAs, (II) a Data and Methodologies section containing strategies used for literature search and study selection, and (III) the Results of the literature review organized according to the three main procurement tasks. The outcome of the first task reviews dsRNA and miRNA pathways in mammals (including humans), birds, fish, arthropods, annelids, molluscs, nematodes, and plants. Eight taxon-dedicated chapters are based on~1,400 cumulative references chosen from~10,000 inspected titles and abstracts. We review conserved and divergent aspects of small RNA pathways and dsRNA responses in animals and plants including structure and function of key proteins as well as four basic mechanisms: genome-encoded posttranscriptional regulations (miRNA), degradation of RNAs by short interfering RNA pools generated from long dsRNA (RNAi), transcriptional silencing, and sequence-independent responses to dsRNA. The outcome of the second task focuses on base pairing between small RNAs and their target RNAs and predictability of biological effects of small RNAs in animals and plants. The outcome of the last task reviews methodology, siRNA pools, and movement of small RNAs in plants. Potential transfer of small RNAs between species and circulating miRNAs in mammals is described in the final chapter.

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Section: Human Ago1 and Ago2 Structuresmentioning

confidence: 77%

Section: Ago2 Structure and Functionmentioning

confidence: 99%

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Literature review of baseline information to support the risk assessment of RNAi‐based GM plants

Pačes

Nič²,

Novotný³

et al. 2017

EFS3

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“…With the ability to reproducibly purify unbound hAgos [84,90] and load them with specific guides [84,90], it became apparent that this binding confers stability to not only to the guide [65,90,91,92] but also Ago itself [90]. Moreover, this binding holds the guide RNA in a conformation that is consistent in all observed structures; this is particularly evident and critical in the seed region [61].…”

Section: Hhmi Author Manuscriptmentioning

confidence: 86%

“…Recent biochemical and structural studies of hAgos have identified determinants of Argonaute slicer activity that extend beyond the active site. These are most notably in an adjacent loop to the active site and in the N domain [84][85][86][87][88]. Moreover, the activity of Agos can be modulated through post-translational modifications including proline hydroxylation that increases slicing activity, sumoylation that increases protein stability, ADP-ribosylation that relieves both slicing and translation repression, and phosphorylation that can either enhance or inhibit silencing efficacy (reviewed in [89]).…”

mentioning

confidence: 99%

From guide to target: molecular insights into eukaryotic RNA-interference machinery

Ipsaro

Joshua‐Tor

2015

Nat Struct Mol Biol

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218

144

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Since its relatively recent discovery, RNA interference (RNAi) has emerged as a potent, specific, and ubiquitous means of gene regulation. Through a number of pathways that are conserved from yeast to humans, small non-coding RNAs direct molecular machinery to silence gene expression. In this review, we focus on mechanisms and structures that govern RNA silencing in higher organisms. In addition to highlighting recent advances, parallels and differences between RNAi pathways are discussed. Together, the studies reviewed herein reveal the versatility and programmability of RNA-induced Silencing Complexes (RISCs) and emphasize the importance of both upstream biogenesis and downstream silencing factors. Discovery and Biological Perspectives of RNA interferenceRNAi was first described by Fire and Mello in the 1990s when, in an attempt to use antisense RNA to down-regulate gene expression, they observed that double-stranded RNA (dsRNA) was more potent than sense or anti-sense RNA alone [1]. This seminal work boasted robust and specific gene knock down in addition to coining the term "RNA interference" (RNAi). Shortly beforehand, the discovery of individual regulatory RNAs in C. elegans hinted that small, non-coding RNAs might be a pervasive means of gene regulation in higher organisms [2,3]. In the following decade, with the mechanistic insight of Fire and Mello's work in hand, this idea was confirmed and it is now accepted that wellover 1,000 small RNAs are encoded in the human genome that may regulate over 60% of our genes [4,5]. It also became apparent that several seemingly disconnected phenomena are variations of RNAi-type pathways including co-suppression in plants, DNA elimination in Tetrahymena, and quelling in Neurospora [6]. The prevalence of RNAi is impressive and its importance is underscored by the fact that RNAi dysfunction is associated with numerous diseases and disorders including neurological maladies, cancers, and infertility.Shortly after the initial description of RNAi phenomenology, a burst of genetic, biochemical, biophysical, and bioinformatic efforts laid a strong foundation for identifying the molecular pathways, players, and parameters that govern silencing via RNAi. Work from Reprints and permissions information is available online at http://www.nature.com/reprints/index.html. HHMI Author ManuscriptHHMI Author Manuscript HHMI Author Manuscript numerous groups defined the molecular apparatus of RNAi as RISC (RNA-induced Silencing Complex), a ribonucleoprotein complex minimally comprised of a small singlestranded RNA (~20-31 nucleotides) and an Argonaute protein which serves as the effector molecule (reviewed in [7]). In this configuration, the loaded "guide" RNA acts as a specificity determinant that directs Argonaute and any other associated machinery to the target. The guide-loaded Argonaute platform underlies every example in the expansive array of known RNAi pathways in eukaryotes regardless of the source of the guide (structured loci, transposons, viral, etc.), the machinery ...

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Complex congenital cardiovascular anomaly in a patient with AGO1‐associated disorder

Takagi

Ono

Kumaki

et al. 2022

American J of Med Genetics Pt A

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Pathogenic AGO1 variants have been associated with neurodevelopmental disorders, including autism spectrum disorder, developmental delay, intellectual disability, and dysmorphic facial appearance. In mammalian models, defects in microRNA (miRNA) biogenesis are associated with congenital heart disease and dilated cardiomyopathy. We describe the case of a patient with partial anomalous pulmonary venous return, hypoplastic left lung, bilateral pulmonary sequestration, and dilated myocardiopathy. We identified a de novo pathogenic variant of AGO1, which encodes an Argonaute protein forming a gene-silencing complex with microRNAs.The patient was diagnosed with dilated cardiomyopathy with no apparent cause at 3 years of age. She was started on enalapril and carvedilol, and her heart failure was well controlled. We expanded the AGO1-associated phenotype to include complex congenital cardiovascular anomaly and dilated cardiomyopathy in humans.

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The Making of a Slicer: Activation of Human Argonaute-1

Cited by 128 publications

References 38 publications

Literature review of baseline information to support the risk assessment of RNAi‐based GM plants

Literature review of baseline information to support the risk assessment of RNAi‐based GM plants

From guide to target: molecular insights into eukaryotic RNA-interference machinery

Complex congenital cardiovascular anomaly in a patient with AGO1‐associated disorder

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