Hillen, Hauke S.

[["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","1082"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Cell"],["dc.bibliographiccitation.lastpage","1093"],["dc.bibliographiccitation.volume","171"],["dc.contributor.author","Hillen, Hauke S."],["dc.contributor.author","Parshin, Andrey V."],["dc.contributor.author","Agaronyan, Karen"],["dc.contributor.author","Morozov, Yaroslav I."],["dc.contributor.author","Graber, James J."],["dc.contributor.author","Chernev, Aleksandar"],["dc.contributor.author","Schwinghammer, Kathrin"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Anikin, Michael"],["dc.contributor.author","Cramer, Patrick"],["dc.contributor.author","Temiakov, Dmitry"],["dc.date.accessioned","2018-01-09T12:26:24Z"],["dc.date.available","2018-01-09T12:26:24Z"],["dc.date.issued","2017"],["dc.description.abstract","In human mitochondria, transcription termination events at a G-quadruplex region near the replication origin are thought to drive replication of mtDNA by generation of an RNA primer. This process is suppressed by a key regulator of mtDNA-the transcription factor TEFM. We determined the structure of an anti-termination complex in which TEFM is bound to transcribing mtRNAP. The structure reveals interactions of the dimeric pseudonuclease core of TEFM with mobile structural elements in mtRNAP and the nucleic acid components of the elongation complex (EC). Binding of TEFM to the DNA forms a downstream \"sliding clamp,\" providing high processivity to the EC. TEFM also binds near the RNA exit channel to prevent formation of the RNA G-quadruplex structure required for termination and thus synthesis of the replication primer. Our data provide insights into target specificity of TEFM and mechanisms by which it regulates the switch between transcription and replication of mtDNA."],["dc.identifier.doi","10.1016/j.cell.2017.09.035"],["dc.identifier.pmid","29033127"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11586"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1097-4172"],["dc.title","Mechanism of Transcription Anti-termination in Human Mitochondria"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","712-716"],["dc.bibliographiccitation.issue","7839"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","716"],["dc.bibliographiccitation.volume","588"],["dc.contributor.author","Bonekamp, Nina A."],["dc.contributor.author","Peter, Bradley"],["dc.contributor.author","Hillen, Hauke S."],["dc.contributor.author","Felser, Andrea"],["dc.contributor.author","Bergbrede, Tim"],["dc.contributor.author","Choidas, Axel"],["dc.contributor.author","Horn, Moritz"],["dc.contributor.author","Unger, Anke"],["dc.contributor.author","Di Lucrezia, Raffaella"],["dc.contributor.author","Atanassov, Ilian"],["dc.contributor.author","Li, Xinping"],["dc.contributor.author","Koch, Uwe"],["dc.contributor.author","Menninger, Sascha"],["dc.contributor.author","Boros, Joanna"],["dc.contributor.author","Habenberger, Peter"],["dc.contributor.author","Giavalisco, Patrick"],["dc.contributor.author","Cramer, Patrick"],["dc.contributor.author","Denzel, Martin S."],["dc.contributor.author","Nussbaumer, Peter"],["dc.contributor.author","Klebl, Bert"],["dc.contributor.author","Falkenberg, Maria"],["dc.contributor.author","Gustafsson, Claes M."],["dc.contributor.author","Larsson, Nils-Göran"],["dc.date.accessioned","2022-02-21T14:38:53Z"],["dc.date.available","2022-02-21T14:38:53Z"],["dc.date.issued","2020"],["dc.description.abstract","Altered expression of mitochondrial DNA (mtDNA) occurs in ageing and a range of human pathologies (for example, inborn errors of metabolism, neurodegeneration and cancer). Here we describe first-in-class specific inhibitors of mitochondrial transcription (IMTs) that target the human mitochondrial RNA polymerase (POLRMT), which is essential for biogenesis of the oxidative phosphorylation (OXPHOS) system1-6. The IMTs efficiently impair mtDNA transcription in a reconstituted recombinant system and cause a dose-dependent inhibition of mtDNA expression and OXPHOS in cell lines. To verify the cellular target, we performed exome sequencing of mutagenized cells and identified a cluster of amino acid substitutions in POLRMT that cause resistance to IMTs. We obtained a cryo-electron microscopy (cryo-EM) structure of POLRMT bound to an IMT, which further defined the allosteric binding site near the active centre cleft of POLRMT. The growth of cancer cells and the persistence of therapy-resistant cancer stem cells has previously been reported to depend on OXPHOS7-17, and we therefore investigated whether IMTs have anti-tumour effects. Four weeks of oral treatment with an IMT is well-tolerated in mice and does not cause OXPHOS dysfunction or toxicity in normal tissues, despite inducing a strong anti-tumour response in xenografts of human cancer cells. In summary, IMTs provide a potent and specific chemical biology tool to study the role of mtDNA expression in physiology and disease."],["dc.identifier.doi","10.1038/s41586-020-03048-z"],["dc.identifier.pmid","33328633"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/100151"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/105"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/19"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["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","1476-4687"],["dc.relation.issn","0028-0836"],["dc.relation.workinggroup","RG Cramer"],["dc.relation.workinggroup","RG Hillen (Structure and Function of Molecular Machines)"],["dc.title","Small-molecule inhibitors of human mitochondrial DNA transcription"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","754"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Nature Structural & Molecular Biology"],["dc.bibliographiccitation.lastpage","765"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Hillen, Hauke S."],["dc.contributor.author","Temiakov, Dmitry"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2022-03-01T11:46:02Z"],["dc.date.available","2022-03-01T11:46:02Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1038/s41594-018-0122-9"],["dc.identifier.pii","122"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103537"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1545-9985"],["dc.relation.issn","1545-9993"],["dc.rights.uri","http://www.springer.com/tdm"],["dc.title","Structural basis of mitochondrial transcription"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","713"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Nature Structural & Molecular Biology"],["dc.bibliographiccitation.lastpage","723"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Bhatta, Arjun"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Cramer, Patrick"],["dc.contributor.author","Hillen, Hauke S."],["dc.date.accessioned","2021-10-01T09:57:57Z"],["dc.date.available","2021-10-01T09:57:57Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Human mitochondrial transcripts contain messenger and ribosomal RNAs flanked by transfer RNAs (tRNAs), which are excised by mitochondrial RNase (mtRNase) P and Z to liberate all RNA species. In contrast to nuclear or bacterial RNase P, mtRNase P is not a ribozyme but comprises three protein subunits that carry out RNA cleavage and methylation by unknown mechanisms. Here, we present the cryo-EM structure of human mtRNase P bound to precursor tRNA, which reveals a unique mechanism of substrate recognition and processing. Subunits TRMT10C and SDR5C1 form a subcomplex that binds conserved mitochondrial tRNA elements, including the anticodon loop, and positions the tRNA for methylation. The endonuclease PRORP is recruited and activated through interactions with its PPR and nuclease domains to ensure precise pre-tRNA cleavage. The structure provides the molecular basis for the first step of RNA processing in human mitochondria."],["dc.identifier.doi","10.1038/s41594-021-00637-y"],["dc.identifier.pii","637"],["dc.identifier.pmid","34489609"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89952"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/337"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/154"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/9"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-469"],["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","Structural basis of RNA processing by human mitochondrial RNase P"],["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","1072"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Cell"],["dc.bibliographiccitation.lastpage","1081"],["dc.bibliographiccitation.volume","171"],["dc.contributor.author","Hillen, Hauke S."],["dc.contributor.author","Morozov, Yaroslav I."],["dc.contributor.author","Sarfallah, Azadeh"],["dc.contributor.author","Temiakov, Dmitry"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2018-01-09T11:46:57Z"],["dc.date.available","2018-01-09T11:46:57Z"],["dc.date.issued","2017"],["dc.description.abstract","Transcription in human mitochondria is driven by a single-subunit, factor-dependent RNA polymerase (mtRNAP). Despite its critical role in both expression and replication of the mitochondrial genome, transcription initiation by mtRNAP remains poorly understood. Here, we report crystal structures of human mitochondrial transcription initiation complexes assembled on both light and heavy strand promoters. The structures reveal how transcription factors TFAM and TFB2M assist mtRNAP to achieve promoter-dependent initiation. TFAM tethers the N-terminal region of mtRNAP to recruit the polymerase to the promoter whereas TFB2M induces structural changes in mtRNAP to enable promoter opening and trapping of the DNA non-template strand. Structural comparisons demonstrate that the initiation mechanism in mitochondria is distinct from that in the well-studied nuclear, bacterial, or bacteriophage transcription systems but that similarities are found on the topological and conceptual level. These results provide a framework for studying the regulation of gene expression and DNA replication in mitochondria."],["dc.identifier.doi","10.1016/j.cell.2017.10.036"],["dc.identifier.pmid","29149603"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11582"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1097-4172"],["dc.title","Structural Basis of Mitochondrial Transcription Initiation"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","279"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Kokic, Goran"],["dc.contributor.author","Hillen, Hauke S."],["dc.contributor.author","Tegunov, Dimitry"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Seitz, Florian"],["dc.contributor.author","Schmitzova, Jana"],["dc.contributor.author","Farnung, Lucas"],["dc.contributor.author","Siewert, Aaron"],["dc.contributor.author","Höbartner, Claudia"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2021-08-12T07:44:55Z"],["dc.date.available","2021-08-12T07:44:55Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Remdesivir is the only FDA-approved drug for the treatment of COVID-19 patients. The active form of remdesivir acts as a nucleoside analog and inhibits the RNA-dependent RNA polymerase (RdRp) of coronaviruses including SARS-CoV-2. Remdesivir is incorporated by the RdRp into the growing RNA product and allows for addition of three more nucleotides before RNA synthesis stalls. Here we use synthetic RNA chemistry, biochemistry and cryo-electron microscopy to establish the molecular mechanism of remdesivir-induced RdRp stalling. We show that addition of the fourth nucleotide following remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation. This translocation barrier causes retention of the RNA 3ʹ-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RdRp. In the structure of the remdesivir-stalled state, the 3ʹ-nucleotide of the RNA product is matched and located with the template base in the active center, and this may impair proofreading by the viral 3ʹ-exonuclease. These mechanistic insights should facilitate the quest for improved antivirals that target coronavirus replication."],["dc.identifier.doi","10.1038/s41467-020-20542-0"],["dc.identifier.pii","20542"],["dc.identifier.pmid","33436624"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88330"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/113"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/17"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-448"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["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","2041-1723"],["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 SARS-CoV-2 polymerase stalling by remdesivir"],["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","1525"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Cell"],["dc.bibliographiccitation.lastpage","1536"],["dc.bibliographiccitation.volume","179"],["dc.contributor.author","Hillen, Hauke S."],["dc.contributor.author","Bartuli, Julia"],["dc.contributor.author","Grimm, Clemens"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Bedenk, Kristina"],["dc.contributor.author","Szalay, Aladar A"],["dc.contributor.author","Fischer, Utz"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2020-04-02T14:06:45Z"],["dc.date.available","2020-04-02T14:06:45Z"],["dc.date.issued","2019-12-12"],["dc.description.abstract","Poxviruses use virus-encoded multisubunit RNA polymerases (vRNAPs) and RNA-processing factors to generate m7G-capped mRNAs in the host cytoplasm. In the accompanying paper, we report structures of core and complete vRNAP complexes of the prototypic Vaccinia poxvirus (Grimm et al., 2019; in this issue of Cell). Here, we present the cryo-electron microscopy (cryo-EM) structures of Vaccinia vRNAP in the form of a transcribing elongation complex and in the form of a co-transcriptional capping complex that contains the viral capping enzyme (CE). The trifunctional CE forms two mobile modules that bind the polymerase surface around the RNA exit tunnel. RNA extends from the vRNAP active site through this tunnel and into the active site of the CE triphosphatase. Structural comparisons suggest that growing RNA triggers large-scale rearrangements on the surface of the transcription machinery during the transition from transcription initiation to RNA capping and elongation. Our structures unravel the basis for synthesis and co-transcriptional modification of poxvirus RNA."],["dc.identifier.doi","10.1016/j.cell.2019.11.023"],["dc.identifier.pmid","31835031"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/63541"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/32"],["dc.language.iso","en"],["dc.notes","Research funded by Deutsche Forschungsgemeinschaft | Volkswagen Foundation | Excellence Strategy (EXC 2067/1- 390729940) | European Research Council Advanced Investigator Grant TRANSREGULON (693023)"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1097-4172"],["dc.relation.issn","0092-8674"],["dc.relation.workinggroup","RG Cramer"],["dc.relation.workinggroup","RG Hillen (Structure and Function of Molecular Machines)"],["dc.title","Structural Basis of Poxvirus Transcription: Transcribing and Capping Vaccinia Complexes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","154-156"],["dc.bibliographiccitation.issue","7819"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","156"],["dc.bibliographiccitation.volume","584"],["dc.contributor.author","Hillen, Hauke S."],["dc.contributor.author","Kokic, Goran"],["dc.contributor.author","Farnung, Lucas"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Tegunov, Dimitry"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2022-02-21T13:20:58Z"],["dc.date.available","2022-02-21T13:20:58Z"],["dc.date.issued","2020"],["dc.description.abstract","The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses an RNA-dependent RNA polymerase (RdRp) for the replication of its genome and the transcription of its genes1-3. Here we present a cryo-electron microscopy structure of the SARS-CoV-2 RdRp in an active form that mimics the replicating enzyme. The structure comprises the viral proteins non-structural protein 12 (nsp12), nsp8 and nsp7, and more than two turns of RNA template-product duplex. The active-site cleft of nsp12 binds to the first turn of RNA and mediates RdRp activity with conserved residues. Two copies of nsp8 bind to opposite sides of the cleft and position the second turn of RNA. Long helical extensions in nsp8 protrude along exiting RNA, forming positively charged 'sliding poles'. These sliding poles can account for the known processivity of RdRp that is required for replicating the long genome of coronaviruses3. Our results enable a detailed analysis of the inhibitory mechanisms that underlie the antiviral activity of substances such as remdesivir, a drug for the treatment of coronavirus disease 2019 (COVID-19)4."],["dc.identifier.doi","10.1038/s41586-020-2368-8"],["dc.identifier.pmid","32438371"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/100148"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/44"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/22"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["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","1476-4687"],["dc.relation.issn","0028-0836"],["dc.relation.workinggroup","RG Hillen (Structure and Function of Molecular Machines)"],["dc.relation.workinggroup","RG Cramer"],["dc.title","Structure of replicating SARS-CoV-2 polymerase"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e2009329118"],["dc.bibliographiccitation.issue","15"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.volume","118"],["dc.contributor.author","Hillen, Hauke S."],["dc.contributor.author","Markov, Dmitriy A."],["dc.contributor.author","Wojtas, Ireneusz D."],["dc.contributor.author","Hofmann, Katharina B."],["dc.contributor.author","Lidschreiber, Michael"],["dc.contributor.author","Cowan, Andrew T."],["dc.contributor.author","Jones, Julia L."],["dc.contributor.author","Temiakov, Dmitry"],["dc.contributor.author","Cramer, Patrick"],["dc.contributor.author","Anikin, Michael"],["dc.date.accessioned","2021-06-01T09:41:49Z"],["dc.date.available","2021-06-01T09:41:49Z"],["dc.date.issued","2021"],["dc.description.abstract","Stabilization of messenger RNA is an important step in posttranscriptional gene regulation. In the nucleus and cytoplasm of eukaryotic cells it is generally achieved by 5′ capping and 3′ polyadenylation, whereas additional mechanisms exist in bacteria and organelles. The mitochondrial mRNAs in the yeast Saccharomyces cerevisiae comprise a dodecamer sequence element that confers RNA stability and 3′-end processing via an unknown mechanism. Here, we isolated the protein that binds the dodecamer and identified it as Rmd9, a factor that is known to stabilize yeast mitochondrial RNA. We show that Rmd9 associates with mRNA around dodecamer elements in vivo and that recombinant Rmd9 specifically binds the element in vitro. The crystal structure of Rmd9 bound to its dodecamer target reveals that Rmd9 belongs to the family of pentatricopeptide (PPR) proteins and uses a previously unobserved mode of specific RNA recognition. Rmd9 protects RNA from degradation by the mitochondrial 3′-exoribonuclease complex mtEXO in vitro, indicating that recognition and binding of the dodecamer element by Rmd9 confers stability to yeast mitochondrial mRNAs."],["dc.identifier.doi","10.1073/pnas.2009329118"],["dc.identifier.pmid","33876744"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85051"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/248"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/143"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/14"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["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","1091-6490"],["dc.relation.issn","0027-8424"],["dc.relation.workinggroup","RG Cramer"],["dc.relation.workinggroup","RG Hillen (Structure and Function of Molecular Machines)"],["dc.title","The pentatricopeptide repeat protein Rmd9 recognizes the dodecameric element in the 3′-UTRs of yeast mitochondrial mRNAs"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]