A Novel Open-Barrel Structure of Octameric Translin Reveals a Potential RNA Entryway

Eliahoo, Elad; Marx, A.; Manor, Haim; Alian, Akram

doi:10.1016/j.jmb.2014.11.013

Cited by 5 publications

(5 citation statements)

References 35 publications

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“…One plausible substrate entryway is revealed by the apo- Ne C3PO structures, which adopts the open form and has one wide gap between the two TraxL subunits (Figure 5B). In light of the recently reported open form Hs Tsn structure (34), our apo- and complex structures of Ne C3PO suggested that ‘conformational switching’ may be a common feature of the translin superfamily proteins. Though it has not been captured in any crystal structure of eukaryotic C3PO, we speculated that the eukaryotic complexes may also adopt the open football form during substrate loading.…”

Section: Discussionmentioning

confidence: 55%

“…Similar to Af C3PO:dsRNA complex structure, the apo-structures of Hs C3PO and Af C3PO also adopt the closed football-like shape. Two distinct mechanisms were previously proposed for the formation of the catalytic C3PO:substrate complex: one is the ‘dissociation and reassembly’ model (12) and the other is the ‘conformational switching’ model (34). However, the conformational changes associated with the substrate entering (or product releasing from) the inner cavity (where the catalytic sites locate) of C3PO remain elusive.…”

Section: Introductionmentioning

confidence: 99%

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Structural basis for single-stranded RNA recognition and cleavage by C3PO

et al. 2016

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Translin and translin-associated factor-x are highly conserved in eukaroytes; they can form heteromeric complexes (known as C3POs) and participate in various nucleic acid metabolism pathways. In humans and Drosophila, C3POs cleave the fragmented siRNA passenger strands and facilitate the activation of RNA-induced silencing complex, the effector complex of RNA interference (RNAi). Here, we report three crystal structures of Nanoarchaeum equitans (Ne) C3PO. The apo-NeC3PO structure adopts an open form and unravels a potential substrates entryway for the first time. The NeC3PO:ssRNA and NeC3PO:ssDNA complexes fold like closed football with the substrates captured at the inner cavities. The NeC3PO:ssRNA structure represents the only catalytic form C3PO complex available to date; with mutagenesis and in vitro cleavage assays, the structure provides critical insights into the substrate binding and the two-cation-assisted catalytic mechanisms that are shared by eukaryotic C3POs. The work presented here further advances our understanding on the RNAi pathway.

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Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Structural basis for single-stranded RNA recognition and cleavage by C3PO

et al. 2016

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“…We have shown that PLCβ binds to an external site on TRAX or between the two TRAX subunits of C3PO and this binding inhibits activity . Oligonucleotides bind in a central cavity between a translin tetramer and a translin‐TRAX dimer that may involve a partial opening of the octamer with reassembly around the substrate . Our FRET studies show a reduced distance between the TRAX subunits with oligonucleotide binding consistent with a clamping of the back end of the octamer.…”

Section: Discussionmentioning

confidence: 60%

Regulation of the activity of the promoter of RNA‐induced silencing, C3PO

et al. 2017

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RNA-induced silencing is a process which allows cells to regulate the synthesis of specific proteins. RNA silencing is promoted by the protein C3PO (component 3 of RISC). We have previously found that phospholipase Cβ, which increases intracellular calcium levels in response to specific G protein signals, inhibits C3PO activity towards certain genes. Understanding the parameters that control C3PO activity and which genes are impacted by G protein activation would help predict which genes are more vulnerable to downregulation. Here, using a library of 10 oligonucleotides, we show that C3PO binds oligonucleotides with structural specificity but little sequence specificity. Alternately, C3PO hydrolyzes oligonucleotides with a rate that is sensitive to substrate stability. Importantly, we find that oligonucleotides with higher Tm values are inhibited by bound PLCβ. This finding is supported by microarray analysis in cells over-expressing PLCβ1. Taken together, this study allows predictions of the genes whose post-transcriptional regulation is responsive to the G protein/phospholipase Cβ/calcium signaling pathway.

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“…Subsequent molecular analysis revealed that translin binds to RNA as well as ssDNA, and participates in transcriptional regulation or mRNA processing . The findings also demonstrated involvement of translin in microtubule‐dependent mRNA transport.…”

Section: Identification and Characterization Of Translinmentioning

confidence: 94%

Mesenchymal cell differentiation and diseases: involvement of translin/TRAX complexes and associated proteins

Kasai

Ishida

Nakahara

et al. 2018

Annals of the New York Academy of Sciences

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Translin and translin-associated factor X (translin/TRAX) proteins have been implicated in a variety of cellular activities central to nucleic acid metabolism. Accumulating evidence indicates that translin/TRAX complexes participate in processes ensuring the replication of DNA, as well as cell division. Significant progress has been made in understanding the roles of translin/TRAX complexes in RNA metabolism, such as through RNA-induced silencing complex activation or the microRNA depletion that occurs in Dicer deficiency. At the cellular level, translin-deficient (Tsn ) mice display delayed endochondral ossification or progressive bone marrow failure with ectopic osteogenesis and adipogenesis, suggesting involvement in mesenchymal cell differentiation. In this review, we summarize the molecular and cellular functions of translin homo-octamer and translin/TRAX hetero-octamer. Finally, we discuss the multifaceted roles of translin, TRAX, and associated proteins in the healthy and disease states.

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A Novel Open-Barrel Structure of Octameric Translin Reveals a Potential RNA Entryway

Cited by 5 publications

References 35 publications

Structural basis for single-stranded RNA recognition and cleavage by C3PO

Structural basis for single-stranded RNA recognition and cleavage by C3PO

Regulation of the activity of the promoter of RNA‐induced silencing, C3PO

Mesenchymal cell differentiation and diseases: involvement of translin/TRAX complexes and associated proteins

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