Dynamics of WD-repeat containing proteins in SSU processome components

Wada, Kouko; Sato, Manae; Araki, Nanase; Kumeta, Masahiro; Hirai, Yoshimasa; Horigome, Tsuneyoshi

doi:10.1139/bcb-2014-0007

Cited by 15 publications

(8 citation statements)

References 30 publications

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“…We therefore became interested in the SSU processome components that were identified as expATXN2 RBPs. Out of the five SSU components 51, 52 that are potential expATXN2 interactors, we selected TBL3 (transducin β-like protein 3) for further analysis, as we were interested in RNA mediated disease mechanisms shared by both SCA2 and HD, and by the same method, TBL3 appeared to interact with the expanded Huntingtin ( expHTT ) transcript as well (Fig. 3B-C), and has a relatively greater number of peptide hits and percentage of protein coverage, compared with other SSU components identified by MS (Table S1), though the number of peptide hits does not always imply stronger interaction 53 .…”

Section: Resultsmentioning

confidence: 99%

RNA toxicity and perturbation of rRNA processing in spinocerebellar ataxia type 2

Moulick

Feng

et al. 2021

Preprint

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BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease caused by expansion of a CAG repeat in Ataxin-2 (ATXN2) gene. The mutant ATXN2 protein with a polyglutamine tract is known to be toxic and contributes to the SCA2 pathogenesis. OBJECTIVE: Here we tested the hypothesis that the mutant ATXN2 transcript with an expanded CAG repeat (expATXN2) is also toxic and contributes to SCA2 pathogenesis. METHODS: The toxic effect of expATXN2 transcripts on SK-N-MC neuroblastoma cells and primary mouse cortical neurons was evaluated by caspase 3/7 activity and nuclear condensation assay, respectively. RNA immunoprecipitation assay was performed to identify RNA binding proteins (RBPs) that bind to expATXN2 RNA. Quantitative PCR was used to examine if rRNA processing is disrupted in SCA2 and Huntington disease (HD) human brain tissue. RESULTS: expATXN2 RNA induces neuronal cell death, and aberrantly interacts with RBPs involved in RNA metabolism. One of the RBPs, transducin beta-like protein 3 (TBL3), involved in rRNA processing, binds to both expATXN2 and expanded huntingtin (expHTT) RNA in vitro. rRNA processing is disrupted in both SCA2 and HD human brain tissue. CONCLUSION: These findings provide the first evidence of a contributory role of expATXN2 transcripts in SCA2 pathogenesis, and further support the role expHTT transcripts in HD pathogenesis. The disruption of rRNA processing, mediated by aberrant interaction of RBPs with expATXN2 and expHTT transcripts, suggest a point of convergence in the pathogeneses of repeat expansion diseases with potential therapeutic implications.

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Section: Resultsmentioning

confidence: 99%

RNA toxicity and perturbation of rRNA processing in spinocerebellar ataxia type 2

Moulick

Feng

et al. 2021

Preprint

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“…NOL10 and NGDN have both been identified as components of the nucleolar proteome (40). NOL10 is a WD40 domain-containing protein enriched in the granular component of nucleoli (45). Also GFP-tagged NGDN has been shown to localize to nucleoli (46).…”

Section: Resultsmentioning

confidence: 99%

Human AATF/Che-1 forms a nucleolar protein complex with NGDN and NOL10 required for 40S ribosomal subunit synthesis

Bammert

Jonas

Ungricht

et al. 2016

Nucleic Acids Research

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Mammalian AATF/Che-1 is essential for embryonic development, however, the underlying molecular mechanism is unclear. By immunoprecipitation of human AATF we discovered that AATF forms a salt-stable protein complex together with neuroguidin (NGDN) and NOL10, and demonstrate that the AATF-NGDN-NOL10 (ANN) complex functions in ribosome biogenesis. All three ANN complex members localize to nucleoli and display a mutual dependence with respect to protein stability. Mapping of protein-protein interaction domains revealed the importance of both the evolutionary conserved WD40 repeats in NOL10 and the UTP3/SAS10 domain in NGDN for complex formation. Functional analysis showed that the ANN complex supports nucleolar steps of 40S ribosomal subunit biosynthesis. All complex members were required for 18S rRNA maturation and their individual depletion affected the same nucleolar cleavage steps in the 5′ETS and ITS1 regions of the ribosomal RNA precursor. Collectively, we identified the ANN complex as a novel functional module supporting the nucleolar maturation of 40S ribosomal subunits. Our data help to explain the described role of AATF in cell proliferation during mouse development as well as its requirement for malignant tumor growth.

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“…An example of a novel RBP, predicted correctly as NA-binding by BindUP, is Nol10. Nol10 is a WD-repeat nuclear protein with an unclear function, previously known to bind protein complexes in the nucleoli ( 47 ) and recently shown to bind RNA in the high throughput interactome capture experiments ( 5 , 7 , 8 ). We predicted the structure of its two domains using I-TASSER ( 41 ) and further submitted them to BindUP.…”

Section: Resultsmentioning

confidence: 99%

BindUP: a web server for non-homology-based prediction of DNA and RNA binding proteins

Paz¹,

Kligun²,

Bengad³

et al. 2016

Nucleic Acids Res

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Gene expression is a multi-step process involving many layers of regulation. The main regulators of the pathway are DNA and RNA binding proteins. While over the years, a large number of DNA and RNA binding proteins have been identified and extensively studied, it is still expected that many other proteins, some with yet another known function, are awaiting to be discovered. Here we present a new web server, BindUP, freely accessible through the website http://bindup.technion.ac.il/, for predicting DNA and RNA binding proteins using a non-homology-based approach. Our method is based on the electrostatic features of the protein surface and other general properties of the protein. BindUP predicts nucleic acid binding function given the proteins three-dimensional structure or a structural model. Additionally, BindUP provides information on the largest electrostatic surface patches, visualized on the server. The server was tested on several datasets of DNA and RNA binding proteins, including proteins which do not possess DNA or RNA binding domains and have no similarity to known nucleic acid binding proteins, achieving very high accuracy. BindUP is applicable in either single or batch modes and can be applied for testing hundreds of proteins simultaneously in a highly efficient manner.

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Dynamics of WD-repeat containing proteins in SSU processome components

Cited by 15 publications

References 30 publications

RNA toxicity and perturbation of rRNA processing in spinocerebellar ataxia type 2

RNA toxicity and perturbation of rRNA processing in spinocerebellar ataxia type 2

Human AATF/Che-1 forms a nucleolar protein complex with NGDN and NOL10 required for 40S ribosomal subunit synthesis

BindUP: a web server for non-homology-based prediction of DNA and RNA binding proteins

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