Höbartner, Claudia

[["dc.bibliographiccitation.journal","Nature Structural & Molecular Biology"],["dc.contributor.author","Kabinger, Florian"],["dc.contributor.author","Stiller, Carina"],["dc.contributor.author","Schmitzová, Jana"],["dc.contributor.author","Dienemann, C."],["dc.contributor.author","Kokic, Goran"],["dc.contributor.author","Hillen, Hauke S."],["dc.contributor.author","Höbartner, Claudia"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2021-09-01T06:42:22Z"],["dc.date.available","2021-09-01T06:42:22Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Molnupiravir is an orally available antiviral drug candidate currently in phase III trials for the treatment of patients with COVID-19. Molnupiravir increases the frequency of viral RNA mutations and impairs SARS-CoV-2 replication in animal models and in humans. Here, we establish the molecular mechanisms underlying molnupiravir-induced RNA mutagenesis by the viral RNA-dependent RNA polymerase (RdRp). Biochemical assays show that the RdRp uses the active form of molnupiravir, β- d - N 4 -hydroxycytidine (NHC) triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RdRp uses the resulting RNA as a template, NHC directs incorporation of either G or A, leading to mutated RNA products. Structural analysis of RdRp–RNA complexes that contain mutagenesis products shows that NHC can form stable base pairs with either G or A in the RdRp active center, explaining how the polymerase escapes proofreading and synthesizes mutated RNA. This two-step mutagenesis mechanism probably applies to various viral polymerases and can explain the broad-spectrum antiviral activity of molnupiravir."],["dc.identifier.doi","10.1038/s41594-021-00651-0"],["dc.identifier.pii","651"],["dc.identifier.pmid","34381216"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89038"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/381"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/171"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/28"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","FOR 2848: Architektur und Heterogenität der inneren mitochondrialen Membran auf der Nanoskala"],["dc.relation","FOR 2848 | St01: Structure and distribution of ribosomes at the inner mitochondrial membrane"],["dc.relation.eissn","1545-9985"],["dc.relation.issn","1545-9993"],["dc.relation.workinggroup","RG Cramer"],["dc.relation.workinggroup","RG Hillen (Structure and Function of Molecular Machines)"],["dc.rights","CC BY 4.0"],["dc.title","Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2004"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","EMBO reports"],["dc.bibliographiccitation.lastpage","2014"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Warda, Ahmed S"],["dc.contributor.author","Kretschmer, Jens"],["dc.contributor.author","Hackert, Philipp"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Höbartner, Claudia"],["dc.contributor.author","Sloan, Katherine E"],["dc.contributor.author","Bohnsack, Markus T"],["dc.date.accessioned","2020-12-10T18:42:38Z"],["dc.date.available","2020-12-10T18:42:38Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.15252/embr.201744940"],["dc.identifier.eissn","1469-3178"],["dc.identifier.issn","1469-221X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78032"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Human METTL16 is a N 6 ‐methyladenosine (m 6 A) methyltransferase that targets pre‐mRNAs and various non‐coding RNAs"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","5859"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Lin, Chao-Chen"],["dc.contributor.author","Seikowski, Jan"],["dc.contributor.author","Perez-Lara, Angel"],["dc.contributor.author","Jahn, Reinhard"],["dc.contributor.author","Höbartner, Claudia"],["dc.contributor.author","Walla, Peter Jomo"],["dc.date.accessioned","2018-11-07T09:31:47Z"],["dc.date.available","2018-11-07T09:31:47Z"],["dc.date.issued","2014"],["dc.description.abstract","Fast synchronous neurotransmitter release is triggered by calcium that activates synaptotagmin-1 (syt-1), resulting in fusion of synaptic vesicles with the presynaptic membrane. Syt-1 possesses two Ca2+-binding C2 domains that tether membranes via interactions with anionic phospholipids. It is capable of crosslinking membranes and has recently been speculated to trigger fusion by decreasing the gap between them. As quantitative information on membrane gaps is key to understanding general cellular mechanisms, including the role of syt-1, we developed a fluorescence-lifetime based inter-membrane distance ruler using membrane-anchored DNAs of various lengths as calibration standards. Wild-type and mutant data provide evidence that full-length syt-1 indeed regulates membrane gaps: without Ca2+, syt-1 maintains membranes at distances of similar to 7-8 nm. Activation with 100 mu M Ca2+ decreases the distance to similar to 5 nm by binding the C2 domains to opposing membranes, respectively. These values reveal that activated syt-1 adjusts membrane distances to the level that promotes SNARE complex assembly."],["dc.identifier.doi","10.1038/ncomms6859"],["dc.identifier.isi","000347683100001"],["dc.identifier.pmid","25500905"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31610"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","2041-1723"],["dc.title","Control of membrane gaps by synaptotagmin-Ca2+ measured with a novel membrane distance ruler"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3720"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Chemistry - A European Journal"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Javadi-Zarnaghi, Fatemeh"],["dc.contributor.author","Hoebartner, Claudia"],["dc.date.accessioned","2018-11-07T10:16:55Z"],["dc.date.available","2018-11-07T10:16:55Z"],["dc.date.issued","2016"],["dc.description.abstract","Catalytic DNAs, also known as deoxyribozymes, are of practical value for the synthesis of structurally or topologically complex RNAs, but little is known about the molecular details of DNA catalysis. We have investigated a deoxyribozyme that catalyzes the formation of a specific intramolecular 2,5-phosphodiester bond to produce lariat RNA, which is an important biological intermediate in eukaryotic mRNA splicing. The results of combinatorial mutation interference analysis (CoMA) allowed us to shrink the catalytic core to 70% of its original length and revealed that the essential part of the deoxyribozyme sequence contained more than 50% guanosines. Nucleotide analogue interference mapping (dNAIM) and dimethyl sulfate interference (DMSi) experiments provided atomic details of individual guanosine functional groups. Additional spectroscopic experiments and structural probing data identified conformational changes upon metal-ion binding and catalysis. Overall, this comprehensive analysis of the DNA-catalyzed reaction has provided specific insights into the synthesis of 2,5-branched RNA, and suggested the general features of deoxyribozymes that catalyze nucleic acid ligation reactions."],["dc.identifier.doi","10.1002/chem.201503238"],["dc.identifier.isi","000371741400002"],["dc.identifier.pmid","26525606"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41133"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","1521-3765"],["dc.relation.issn","0947-6539"],["dc.title","Functional Hallmarks of a Catalytic DNA that Makes Lariat RNA"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","231"],["dc.bibliographiccitation.issue","7585"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","U272"],["dc.bibliographiccitation.volume","529"],["dc.contributor.author","Ponce-Salvatierra, Almudena"],["dc.contributor.author","Wawrzyniak-Turek, Katarzyna"],["dc.contributor.author","Steuerwald, Ulrich"],["dc.contributor.author","Hoebartner, Claudia"],["dc.contributor.author","Pena, Vladimir"],["dc.date.accessioned","2018-11-07T10:19:25Z"],["dc.date.available","2018-11-07T10:19:25Z"],["dc.date.issued","2016"],["dc.description.abstract","Catalysis in biology is restricted to RNA (ribozymes) and protein enzymes, but synthetic biomolecular catalysts can also be made of DNA (deoxyribozymes)(1) or synthetic genetic polymers(2). In vitro selection from synthetic random DNA libraries identified DNA catalysts for various chemical reactions beyond RNA backbone cleavage(3). DNA-catalysed reactions include RNA and DNA ligation in various topologies(4,5), hydrolytic cleavage(6,7) and photorepair of DNA(8), as well as reactions of peptides(9,10) and small molecules(11,12). In spite of comprehensive biochemical studies of DNA catalysts for two decades, fundamental mechanistic understanding of their function is lacking in the absence of three-dimensional models at atomic resolution. Early attempts to solve the crystal structure of an RNA-cleaving deoxyribozyme resulted in a catalytically irrelevant nucleic acid fold(13). Here we report the crystal structure of the RNA-ligating deoxyribozyme 9DB1 (ref. 14) at 2.8 angstrom resolution. The structure captures the ligation reaction in the post-catalytic state, revealing a compact folding unit stabilized by numerous tertiary interactions, and an unanticipated organization of the catalytic centre. Structure-guided mutagenesis provided insights into the basis for regioselectivity of the ligation reaction and allowed remarkable manipulation of substrate recognition and reaction rate. Moreover, the structure highlights how the specific properties of deoxyribose are reflected in the backbone conformation of the DNA catalyst, in support of its intricate three-dimensional organization. The structural principles underlying the catalytic ability of DNA elucidate differences and similarities in DNA versus RNA catalysts, which is relevant for comprehending the privileged position of folded RNA in the prebiotic world and in current organisms."],["dc.description.sponsorship","Max Planck Society"],["dc.identifier.doi","10.1038/nature16471"],["dc.identifier.isi","000368015700041"],["dc.identifier.pmid","26735012"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14049"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41653"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1476-4687"],["dc.relation.issn","0028-0836"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Crystal structure of a DNA catalyst"],["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","3172"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Chemical Science"],["dc.bibliographiccitation.lastpage","3180"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Halbmair, Karin"],["dc.contributor.author","Seikowski, Jan"],["dc.contributor.author","Tkach, Igor"],["dc.contributor.author","Höbartner, Claudia"],["dc.contributor.author","Sezer, Deniz"],["dc.contributor.author","Bennati, Marina"],["dc.date.accessioned","2016-07-05T10:41:32Z"],["dc.date.accessioned","2021-10-27T13:12:28Z"],["dc.date.available","2016-07-05T10:41:32Z"],["dc.date.available","2021-10-27T13:12:28Z"],["dc.date.issued","2016"],["dc.description.abstract","Structural information at atomic resolution of biomolecular assemblies, such as RNA and RNA protein complexes, is fundamental to comprehend biological function. Modern spectroscopic methods offer exceptional opportunities in this direction. Here we present the capability of pulse EPR to report highresolution long-range distances in RNAs by means of a recently developed spin labeled nucleotide, which carries the TEMPO group directly attached to the nucleobase and preserves Watson–Crick base-pairing. In a representative RNA duplex with spin-label separations up to 28 base pairs (z8 nm) we demonstrate that the label allows for a model-free conversion of inter-spin distances into base-pair separation (Dbp) if broadband pulse excitation at Q band frequencies (34 GHz) is applied. The observed distance distribution increases from 0.2 nm for Dbp ¼ 10 to only 0.5 nm for Dbp ¼ 28, consistent with only small deviations from the “ideal” A-form RNA structure. Molecular dynamics (MD) simulations conducted at 20 C show restricted conformational freedom of the label. MD-generated structural deviations from an “ideal” A-RNA geometry help disentangle the contributions of local flexibility of the label and its neighboring nucleobases and global deformations of the RNA double helix to the experimental distance distributions. The study demonstrates that our simple but strategic spin labeling procedure can access detailed structural information on RNAs at atomic resolution over distances that match the size of macromolecular RNA complexes."],["dc.description.sponsorship","DFG Collaborative Research Centre (CRC) [803]; Max Planck Society"],["dc.identifier.doi","10.1039/C5SC04631A"],["dc.identifier.isi","000374859300027"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13415"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91693"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Royal Soc Chemistry"],["dc.relation.issn","2041-6539"],["dc.relation.issn","2041-6520"],["dc.relation.orgunit","Fakultät für Chemie"],["dc.rights","CC BY-NC 3.0"],["dc.rights.access","openAccess"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/3.0"],["dc.subject","long-range distances; RNA; EPR spectroscopy"],["dc.title","High-resolution measurement of long-range distances in RNA: pulse EPR spectroscopy with TEMPO-labeled nucleotides"],["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","1532"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","RNA"],["dc.bibliographiccitation.lastpage","1543"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Haag, Sara"],["dc.contributor.author","Warda, Ahmed S."],["dc.contributor.author","Kretschmer, Jens"],["dc.contributor.author","Guennigmann, Manuel A."],["dc.contributor.author","Hoebartner, Claudia"],["dc.contributor.author","Bohnsack, Markus T."],["dc.date.accessioned","2018-11-07T09:52:51Z"],["dc.date.available","2018-11-07T09:52:51Z"],["dc.date.issued","2015"],["dc.description.abstract","Many cellular RNAs require modification of specific residues for their biogenesis, structure, and function. 5-methylcytosine (m(5)C) is a common chemical modification in DNA and RNA but in contrast to the DNA modifying enzymes, only little is known about the methyltransferases that establish m(5)C modifications in RNA. The putative RNA methyltransferase NSUN6 belongs to the family of Nol1/Nop2/SUN domain (NSUN) proteins, but so far its cellular function has remained unknown. To reveal the target spectrum of human NSUN6, we applied UV crosslinking and analysis of cDNA (CRAC) as well as chemical crosslinking with 5-azacytidine. We found that human NSUN6 is associated with tRNAs and acts as a tRNA methyltransferase. Furthermore, we uncovered tRNACys and tRNAThr as RNA substrates of NSUN6 and identified the cytosine C72 at the 3' end of the tRNA acceptor stem as the target nucleoside. Interestingly, target recognition in vitro depends on the presence of the 3'-CCA tail. Together with the finding that NSUN6 localizes to the cytoplasm and largely colocalizes with marker proteins for the Golgi apparatus and pericentriolar matrix, our data suggest that NSUN6 modifies tRNAs in a late step in their biogenesis."],["dc.identifier.doi","10.1261/rna.051524.115"],["dc.identifier.isi","000359996100002"],["dc.identifier.pmid","26160102"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36208"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cold Spring Harbor Lab Press, Publications Dept"],["dc.relation.issn","1469-9001"],["dc.relation.issn","1355-8382"],["dc.title","NSUN6 is a human RNA methyltransferase that catalyzes formation of m(5)C72 in specific tRNAs"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","37"],["dc.bibliographiccitation.lastpage","58"],["dc.bibliographiccitation.seriesnr","170"],["dc.contributor.author","Javadi-Zarnaghi, Fatemeh"],["dc.contributor.author","Höbartner, Claudia"],["dc.contributor.editor","Seitz, Harald"],["dc.contributor.editor","Stahl, Frank"],["dc.contributor.editor","Walter, Johanna-Gabriela"],["dc.date.accessioned","2021-04-21T11:15:39Z"],["dc.date.available","2021-04-21T11:15:39Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1007/10_2016_59"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84281"],["dc.relation.crisseries","Advances in Biochemical Engineering/Biotechnology"],["dc.relation.doi","10.1007/978-3-030-29646-9"],["dc.relation.eisbn","978-3-030-29646-9"],["dc.relation.isbn","978-3-030-29645-2"],["dc.relation.ispartof","Catalytically Active Nucleic Acids"],["dc.relation.ispartofseries","Advances in Biochemical Engineering/Biotechnology; 170"],["dc.title","Strategies for Characterization of Enzymatic Nucleic Acids"],["dc.type","book_chapter"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","11992"],["dc.bibliographiccitation.issue","88"],["dc.bibliographiccitation.journal","Chemical Communications"],["dc.bibliographiccitation.lastpage","11995"],["dc.bibliographiccitation.volume","53"],["dc.contributor.author","Carrocci, Tucker J."],["dc.contributor.author","Lohe, Lea"],["dc.contributor.author","Ashton, Matthew J."],["dc.contributor.author","Höbartner, Claudia"],["dc.contributor.author","Hoskins, Aaron A."],["dc.date.accessioned","2020-12-10T18:11:15Z"],["dc.date.available","2020-12-10T18:11:15Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1039/C7CC06703H"],["dc.identifier.eissn","1364-548X"],["dc.identifier.issn","1359-7345"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73935"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Debranchase-resistant labeling of RNA using the 10DM24 deoxyribozyme and fluorescent modified nucleotides"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1770"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","RNA"],["dc.bibliographiccitation.lastpage","1779"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Bao, Penghui"],["dc.contributor.author","Höbartner, Claudia"],["dc.contributor.author","Hartmuth, Klaus"],["dc.contributor.author","Lührmann, Reinhard"],["dc.date.accessioned","2020-12-10T18:41:55Z"],["dc.date.available","2020-12-10T18:41:55Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1261/rna.063115.117"],["dc.identifier.eissn","1469-9001"],["dc.identifier.issn","1355-8382"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16996"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77729"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","Yeast Prp2 liberates the 5′ splice site and the branch site adenosine for catalysis of pre-mRNA splicing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]