Thoms, Sven

[["dc.bibliographiccitation.firstpage","1766"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Molecular Biology of the Cell"],["dc.bibliographiccitation.lastpage","1779"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Kaczmarek, Karina"],["dc.contributor.author","Studencka, Maja"],["dc.contributor.author","Meinhardt, Andreas"],["dc.contributor.author","Wieczerzak, Krzysztof"],["dc.contributor.author","Thoms, Sven"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Grzmil, Pawel"],["dc.date.accessioned","2018-11-07T08:56:09Z"],["dc.date.available","2018-11-07T08:56:09Z"],["dc.date.issued","2011"],["dc.description.abstract","Peroxisomal testis-specific 1 gene (Pxt1) is the only male germ cell-specific gene that encodes a peroxisomal protein known to date. To elucidate the role of Pxt1 in spermatogenesis, we generated transgenic mice expressing a c-MYC-PXT1 fusion protein under the control of the PGK2 promoter. Overexpression of Pxt1 resulted in induction of male germ cells' apoptosis mainly in primary spermatocytes, finally leading to male infertility. This prompted us to analyze the proapoptotic character of mouse PXT1, which harbors a BH3-like domain in the N-terminal part. In different cell lines, the overexpression of PXT1 also resulted in a dramatic increase of apoptosis, whereas the deletion of the BH3-like domain significantly reduced cell death events, thereby confirming that the domain is functional and essential for the proapoptotic activity of PXT1. Moreover, we demonstrated that PXT1 interacts with apoptosis regulator BAT3, which, if overexpressed, can protect cells from the PXT1-induced apoptosis. The PXT1-BAT3 association leads to PXT1 relocation from the cytoplasm to the nucleus. In summary, we demonstrated that PXT1 induces apoptosis via the BH3-like domain and that this process is inhibited by BAT3."],["dc.identifier.doi","10.1091/mbc.E09-12-0993"],["dc.identifier.isi","000290515600012"],["dc.identifier.pmid","21460186"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8147"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23074"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Cell Biology"],["dc.relation.issn","1059-1524"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","38"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Communications Biology"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Oleksiievets, Nazar"],["dc.contributor.author","Sargsyan, Yelena"],["dc.contributor.author","Thiele, Jan Christoph"],["dc.contributor.author","Mougios, Nikolaos"],["dc.contributor.author","Sograte-Idrissi, Shama"],["dc.contributor.author","Nevskyi, Oleksii"],["dc.contributor.author","Gregor, Ingo"],["dc.contributor.author","Opazo, Felipe"],["dc.contributor.author","Thoms, Sven"],["dc.contributor.author","Enderlein, Jörg"],["dc.contributor.author","Tsukanov, Roman"],["dc.date.accessioned","2022-01-13T06:27:32Z"],["dc.date.available","2022-01-13T06:27:32Z"],["dc.date.issued","2022-01-11"],["dc.description.abstract","DNA point accumulation for imaging in nanoscale topography (DNA-PAINT) is a powerful super-resolution technique highly suitable for multi-target (multiplexing) bio-imaging. However, multiplexed imaging of cells is still challenging due to the dense and sticky environment inside a cell. Here, we combine fluorescence lifetime imaging microscopy (FLIM) with DNA-PAINT and use the lifetime information as a multiplexing parameter for targets identification. In contrast to Exchange-PAINT, fluorescence lifetime PAINT (FL-PAINT) can image multiple targets simultaneously and does not require any fluid exchange, thus leaving the sample undisturbed and making the use of flow chambers/microfluidic systems unnecessary. We demonstrate the potential of FL-PAINT by simultaneous imaging of up to three targets in a cell using both wide-field FLIM and 3D time-resolved confocal laser scanning microscopy (CLSM). FL-PAINT can be readily combined with other existing techniques of multiplexed imaging and is therefore a perfect candidate for high-throughput multi-target bio-imaging."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.1038/s42003-021-02976-4"],["dc.identifier.pmid","35017652"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/98096"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/392"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/415"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A10: Peroxisomen als modulatorische Einheiten im Herzstoffwechsel und bei Herzinsuffizienz"],["dc.relation.issn","2399-3642"],["dc.relation.orgunit","III. Physikalisches Institut - Biophysik"],["dc.relation.workinggroup","RG Enderlein"],["dc.relation.workinggroup","RG Thoms (Biochemistry and Molecular Medicine)"],["dc.rights","CC BY 4.0"],["dc.title","Fluorescence lifetime DNA-PAINT for multiplexed super-resolution imaging of cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","7809"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.lastpage","13"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Soliman, Kareem"],["dc.contributor.author","Göttfert, Fabian"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Thoms, Sven"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2019-02-27T10:14:35Z"],["dc.date.available","2019-02-27T10:14:35Z"],["dc.date.issued","2018"],["dc.description.abstract","Peroxisomes are ubiquitous cell organelles involved in many metabolic and signaling functions. Their assembly requires peroxins, encoded by PEX genes. Mutations in PEX genes are the cause of Zellweger Syndrome spectrum (ZSS), a heterogeneous group of peroxisomal biogenesis disorders (PBD). The size and morphological features of peroxisomes are below the diffraction limit of light, which makes them attractive for super-resolution imaging. We applied Stimulated Emission Depletion (STED) microscopy to study the morphology of human peroxisomes and peroxisomal protein localization in human controls and ZSS patients. We defined the peroxisome morphology in healthy skin fibroblasts and the sub-diffraction phenotype of residual peroxisomal structures (‘ghosts’) in ZSS patients that revealed a relation between mutation severity and clinical phenotype. Further, we investigated the 70 kDa peroxisomal membrane protein (PMP70) abundance in relationship to the ZSS sub-diffraction phenotype. This work improves the morphological definition of peroxisomes. It expands current knowledge about peroxisome biogenesis and ZSS pathoethiology to the sub-diffraction phenotype including key peroxins and the characteristics of ghost peroxisomes."],["dc.identifier.doi","10.1038/s41598-018-24119-2"],["dc.identifier.pmid","29773809"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15261"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57637"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/210"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A10: Peroxisomen als modulatorische Einheiten im Herzstoffwechsel und bei Herzinsuffizienz"],["dc.relation.issn","2045-2322"],["dc.relation.workinggroup","RG Thoms (Biochemistry and Molecular Medicine)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Super-resolution imaging reveals the sub-diffraction phenotype of Zellweger Syndrome ghosts and wild-type peroxisomes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"],["local.message.claim","2020-08-07T08:23:16.626+0000|||rp114519|||submit_approve|||dc_contributor_author|||None"]]

[["dc.bibliographiccitation.firstpage","259"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Disease Models & Mechanisms"],["dc.bibliographiccitation.lastpage","269"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Quentin, Thomas"],["dc.contributor.author","Steinmetz, Michael"],["dc.contributor.author","Poppe, Andrea"],["dc.contributor.author","Thoms, Sven"],["dc.date.accessioned","2018-11-07T09:12:35Z"],["dc.date.available","2018-11-07T09:12:35Z"],["dc.date.issued","2012"],["dc.description.abstract","Endoplasmic reticulum stress signaling (ERSS) plays an important role in the pathogenesis of diabetes and heart disease. The latter is a common comorbidity of diabetes and worsens patient outcome. Results from clinical studies suggest beneficial effects of metformin - a widely used oral drug for the treatment of type 2 diabetes - on the heart of diabetic patients with heart failure. We therefore analyzed the effect of metformin on ERSS in primary rat cardiomyocytes. We found that metformin activates the PERK-ATF4 but not the ATF6 or IRE1-XBP1 branch in ERSS and leads to a strong upregulation of CHOP mRNA and protein. Surprisingly, long-term induction of CHOP by metformin is not accompanied by apoptosis even though CHOP is regarded to be a mediator of ER-stress-induced apoptosis. In conclusion, metformin induces distinct ER stress pathways in cardiomyocytes and our results indicate that CHOP is not necessarily a mediator of apoptosis. Metformin might exert its cardioprotective effect through selective activation of ERSS pathways in the cardiomyocyte."],["dc.identifier.doi","10.1242/dmm.008110"],["dc.identifier.isi","000302899700012"],["dc.identifier.pmid","22107872"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8178"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26970"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1754-8403"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Metformin differentially activates ER stress signaling pathways without inducing apoptosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","150148"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Open Biology"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Thoms, Sven"],["dc.date.accessioned","2018-11-07T09:49:30Z"],["dc.date.available","2018-11-07T09:49:30Z"],["dc.date.issued","2015"],["dc.description.abstract","Peroxisomes are capable of importing folded and oligomeric proteins. However, it is a matter of dispute whether oligomer import by peroxisomes is the exception or the rule. Here, I argue for a clear distinction between homo-oligomeric proteins that are essentially peroxisomal, and dually localized hetero-oligomers that access the peroxisome by piggyback import, localizing there in limited number, whereas the majority remain in the cytosol. Homo-oligomeric proteins comprise the majority of all peroxisomal matrix proteins. There is evidence that binding by Pex5 in the cytosol can regulate their oligomerization state before import. The hetero-oligomer group is made up of superoxide dismutase and lactate dehydrogenase. These proteins have evolved mechanisms that render import inefficient and retain the majority of proteins in the cytosol."],["dc.identifier.doi","10.1098/rsob.150148"],["dc.identifier.isi","000365030700005"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12622"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35522"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","2046-2441"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Import of proteins into peroxisomes: piggybacking to a new home away from home"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","773"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Nature Genetics"],["dc.bibliographiccitation.lastpage","775"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Henneke, Marco"],["dc.contributor.author","Diekmann, Simone"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Kaiser, Jens"],["dc.contributor.author","Engelbrecht, Volkher"],["dc.contributor.author","Kohlschuetter, Alfried"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Madruga-Garrido, Marcos"],["dc.contributor.author","Mayer, Michele"],["dc.contributor.author","Opitz, Lennart"],["dc.contributor.author","Rodriguez, Diana"],["dc.contributor.author","Rueschendorf, Franz"],["dc.contributor.author","Schumacher, Johannes"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Thoms, Sven"],["dc.contributor.author","Steinfeld, Robert"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:46:53Z"],["dc.date.available","2017-09-07T11:46:53Z"],["dc.date.issued","2009"],["dc.description.abstract","Congenital cytomegalovirus brain infection without symptoms at birth can cause a static encephalopathy with characteristic patterns of brain abnormalities. Here we show that loss-of-function mutations in the gene encoding the RNASET2 glycoprotein lead to cystic leukoencephalopathy, an autosomal recessive disorder with an indistinguishable clinical and neuroradiological phenotype. Congenital cytomegalovirus infection and RNASET2 deficiency may both interfere with brain development and myelination through angiogenesis or RNA metabolism."],["dc.identifier.doi","10.1038/ng.398"],["dc.identifier.gro","3143090"],["dc.identifier.isi","000267786200005"],["dc.identifier.pmid","19525954"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6147"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/565"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1061-4036"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","RNASET2-deficient cystic leukoencephalopathy resembles congenital cytomegalovirus brain infection"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"],["local.message.claim","2020-08-07T08:23:16.626+0000|||rp114519|||submit_approve|||dc_contributor_author|||None"]]

[["dc.bibliographiccitation.firstpage","293"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Trends in Molecular Medicine"],["dc.bibliographiccitation.lastpage","302"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Thoms, Sven"],["dc.contributor.author","Gronborg, Sabine"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:47:25Z"],["dc.date.available","2017-09-07T11:47:25Z"],["dc.date.issued","2009"],["dc.description.abstract","Peroxisomes are no longer regarded as autonomous organelles because evidence for their interplay with other cellular organelles is emerging. Peroxisomes interact with mitochondria in several metabolic pathways, including P-oxidation of fatty acids and the metabolism of reactive oxygen species. Both organelles are in close contact with the endoplasmic reticulum (ER) and share several proteins, including organelle fission factors. Today, the study of peroxisome biogenesis disorders mainly focuses on metabolic defects such as accumulation of very long chain fatty acids or plasmalogen deficiency. In addition to metabolic dysregulation, mitochondria and ER abnormalities have also been observed. Whether these contribute to disease pathology is not yet known, but recent findings suggest that this possibility should be considered. Here, we discuss the potential involvement of organelle interplay in peroxisomal disorders."],["dc.identifier.doi","10.1016/j.molmed.2009.05.002"],["dc.identifier.gro","3143096"],["dc.identifier.isi","000268616800002"],["dc.identifier.pmid","19560974"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6320"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/573"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Sci Ltd"],["dc.relation.issn","1471-4914"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Organelle interplay in peroxisomal disorders"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"],["local.message.claim","2020-08-07T08:23:16.626+0000|||rp114519|||submit_approve|||dc_contributor_author|||None"]]

[["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","PLoS Genetics"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Schueren, Fabian"],["dc.contributor.author","Thoms, Sven"],["dc.date.accessioned","2018-11-07T10:10:57Z"],["dc.date.available","2018-11-07T10:10:57Z"],["dc.date.issued","2016"],["dc.description.abstract","Translational readthrough (TR) has come into renewed focus because systems biology approaches have identified the first human genes undergoing functional translational readthrough (FTR). FTR creates functional extensions to proteins by continuing translation of the mRNA downstream of the stop codon. Here we review recent developments in TR research with a focus on the identification of FTR in humans and the systems biology methods that have spurred these discoveries."],["dc.identifier.doi","10.1371/journal.pgen.1006196"],["dc.identifier.isi","000382394500012"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13705"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39953"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1553-7404"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Functional Translational Readthrough: A Systems Biology Perspective"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e03640"],["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Schueren, Fabian"],["dc.contributor.author","Lingner, Thomas"],["dc.contributor.author","George, Rosemol"],["dc.contributor.author","Hofhuis, Julia"],["dc.contributor.author","Dickel, Corinna"],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Thoms, Sven"],["dc.date.accessioned","2017-09-07T11:45:30Z"],["dc.date.available","2017-09-07T11:45:30Z"],["dc.date.issued","2014"],["dc.description.abstract","Translational readthrough gives rise to low abundance proteins with C-terminal extensions beyond the stop codon. To identify functional translational readthrough, we estimated the readthrough propensity (RTP) of all stop codon contexts of the human genome by a new regression model in silico, identified a nucleotide consensus motif for high RTP by using this model, and analyzed all readthrough extensions in silico with a new predictor for peroxisomal targeting signal type 1 (PTS1). Lactate dehydrogenase B (LDHB) showed the highest combined RTP and PTS1 probability. Experimentally we show that at least 1.6% of the total cellular LDHB getting targeted to the peroxisome by a conserved hidden PTS1. The readthrough-extended lactate dehydrogenase subunit LDHBx can also co-import LDHA, the other LDH subunit into peroxisomes. Peroxisomal LDH is conserved in mammals and likely contributes to redox equivalent regeneration in peroxisomes."],["dc.identifier.doi","10.7554/eLife.03640"],["dc.identifier.gro","3142048"],["dc.identifier.isi","000342090300002"],["dc.identifier.pmid","25247702"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11685"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3967"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elife Sciences Publications Ltd"],["dc.relation.issn","2050-084X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"],["local.message.claim","2020-08-07T08:23:16.626+0000|||rp114519|||submit_approve|||dc_contributor_author|||None"]]

[["dc.bibliographiccitation.firstpage","1006"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Biomolecules"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Schilff, Mirco"],["dc.contributor.author","Sargsyan, Yelena"],["dc.contributor.author","Hofhuis, Julia"],["dc.contributor.author","Thoms, Sven"],["dc.date.accessioned","2021-08-12T07:45:50Z"],["dc.date.available","2021-08-12T07:45:50Z"],["dc.date.issued","2021"],["dc.description.abstract","Premature termination codon (PTC) mutations account for approximately 10% of pathogenic variants in monogenic diseases. Stimulation of translational readthrough, also known as stop codon suppression, using translational readthrough-inducing drugs (TRIDs) may serve as a possible therapeutic strategy for the treatment of genetic PTC diseases. One important parameter governing readthrough is the stop codon context (SCC)—the stop codon itself and the nucleotides in the vicinity of the stop codon on the mRNA. However, the quantitative influence of the SCC on treatment outcome and on appropriate drug concentrations are largely unknown. Here, we analyze the readthrough-stimulatory effect of various readthrough-inducing drugs on the SCCs of five common premature termination codon mutations of PEX5 in a sensitive dual reporter system. Mutations in PEX5, encoding the peroxisomal targeting signal 1 receptor, can cause peroxisomal biogenesis disorders of the Zellweger spectrum. We show that the stop context has a strong influence on the levels of readthrough stimulation and impacts the choice of the most effective drug and its concentration. These results highlight potential advantages and the personalized medicine nature of an SCC-based strategy in the therapy of rare diseases."],["dc.description.abstract","Premature termination codon (PTC) mutations account for approximately 10% of pathogenic variants in monogenic diseases. Stimulation of translational readthrough, also known as stop codon suppression, using translational readthrough-inducing drugs (TRIDs) may serve as a possible therapeutic strategy for the treatment of genetic PTC diseases. One important parameter governing readthrough is the stop codon context (SCC)—the stop codon itself and the nucleotides in the vicinity of the stop codon on the mRNA. However, the quantitative influence of the SCC on treatment outcome and on appropriate drug concentrations are largely unknown. Here, we analyze the readthrough-stimulatory effect of various readthrough-inducing drugs on the SCCs of five common premature termination codon mutations of PEX5 in a sensitive dual reporter system. Mutations in PEX5, encoding the peroxisomal targeting signal 1 receptor, can cause peroxisomal biogenesis disorders of the Zellweger spectrum. We show that the stop context has a strong influence on the levels of readthrough stimulation and impacts the choice of the most effective drug and its concentration. These results highlight potential advantages and the personalized medicine nature of an SCC-based strategy in the therapy of rare diseases."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship","Niedersächsisches Ministerium für Wissenschaft und Kultur"],["dc.description.sponsorship","Horst and Eva-Luise Köhler Foundation"],["dc.description.sponsorship","Deutscher Akademischer Austauschdienst"],["dc.description.sponsorship","Else Kröner-Fresenius-Stiftung"],["dc.identifier.doi","10.3390/biom11071006"],["dc.identifier.pii","biom11071006"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88558"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-448"],["dc.publisher","MDPI"],["dc.relation.eissn","2218-273X"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Stop Codon Context-Specific Induction of Translational Readthrough"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]