Adio, Sarah

[["dc.bibliographiccitation.artnumber","7442"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.lastpage","11"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Adio, Sarah"],["dc.contributor.author","Senyushkina, Tamara"],["dc.contributor.author","Peske, Frank"],["dc.contributor.author","Fischer, Niels"],["dc.contributor.author","Wintermeyer, Wolfgang"],["dc.contributor.author","Rodnina, Marina V."],["dc.date.accessioned","2017-09-07T11:44:23Z"],["dc.date.available","2017-09-07T11:44:23Z"],["dc.date.issued","2015"],["dc.description.abstract","The coupled translocation of transfer RNA and messenger RNA through the ribosome entails large-scale structural rearrangements, including step-wise movements of the tRNAs. Recent structural work has visualized intermediates of translocation induced by elongation factor G (EF-G) with tRNAs trapped in chimeric states with respect to 30S and 50S ribosomal subunits. The functional role of the chimeric states is not known. Here we follow the formation of translocation intermediates by single-molecule fluorescence resonance energy transfer. Using EF-G mutants, a non-hydrolysable GTP analogue, and fusidic acid, we interfere with either translocation or EF-G release from the ribosome and identify several rapidly interconverting chimeric tRNA states on the reaction pathway. EF-G engagement prevents backward transitions early in translocation and increases the fraction of ribosomes that rapidly fluctuate between hybrid, chimeric and posttranslocation states. Thus, the engagement of EF-G alters the energetics of translocation towards a flat energy landscape, thereby promoting forward tRNA movement."],["dc.identifier.doi","10.1038/ncomms8442"],["dc.identifier.gro","3141892"],["dc.identifier.isi","000357176700008"],["dc.identifier.pmid","26072700"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2234"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","2041-1723"],["dc.title","Fluctuations between multiple EF-G-induced chimeric tRNA states during translocation on the ribosome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","919"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","RNA"],["dc.bibliographiccitation.lastpage","922"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Beringer, Malte"],["dc.contributor.author","Adio, Sarah"],["dc.contributor.author","Wintermeyer, Wolfgang"],["dc.contributor.author","Rodnina, Marina"],["dc.date.accessioned","2017-09-07T11:44:19Z"],["dc.date.available","2017-09-07T11:44:19Z"],["dc.date.issued","2003"],["dc.description.abstract","Peptide bond formation on the ribosome is catalyzed by RNA. Kinetic studies using Escherichia coli ribosomes have shown that catalysis (>10(5)-fold overall acceleration) is due to a large part to substrate positioning. However, peptide bond formation is inhibited similar to100-fold by protonation of a ribosomal group with pK(a)=7.5, indicating either a contribution of general acid-base catalysis or inhibition by a pH-dependent conformational change within the active site. The function of a general base has been attributed to A2451 of 23S rRNA, and a charge relay system involving G2447 has been postulated to bring about the extensive pK(a) shift of A2451 implied in the model. Using a rapid kinetic assay, we found that the G2447A mutation, which has essentially no effect on cell growth, lowers the rate of peptide bond formation about 10-fold and does not affect the ionization of the ribosomal group with pK(a)=7.5 taking part in the reaction. This result does not support the proposed charge relay mechanism involving G2447 and the role of A2451 as general base in the catalysis of peptide bond formation."],["dc.identifier.doi","10.1261/rna.5600503"],["dc.identifier.gro","3144082"],["dc.identifier.isi","000184381600002"],["dc.identifier.pmid","12869702"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1666"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cold Spring Harbor Lab Press, Publications Dept"],["dc.relation.issn","1355-8382"],["dc.title","The G2447A mutation does not affect ionization of a ribosomal group taking part in peptide bond formation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e2203567119"],["dc.bibliographiccitation.issue","48"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.volume","119"],["dc.contributor.author","Enders, Marieke"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Adio, Sarah"],["dc.date.accessioned","2022-12-01T08:31:04Z"],["dc.date.available","2022-12-01T08:31:04Z"],["dc.date.issued","2022"],["dc.description.abstract","The DEAH/RHA helicase Prp43 remodels protein–RNA complexes during pre-messenger RNA (mRNA) splicing and ribosome biogenesis. The helicase activity and ATP turnover are intrinsically low and become activated by G-patch (gp) factors in the specific cellular context. The gp motif connects the helicase core to the flexible C-terminal domains, but it is unclear how this affects RecA domain movement during catalysis and the unwinding of RNA substrates. We developed single-molecule Förster Resonance Energy Transfer (smFRET) reporters to study RecA domain movements within Prp43 in real time. Without Pfa1(gp), the domains approach each other adopting predominantly a closed conformation. The addition of Pfa1(gp) induces an open state, which becomes even more prevalent during interaction with RNA. In the open state, Prp43 has reduced contacts with bound nucleotide and shows rapid adenosine diphosphate (ADP) release accelerating the transition from the weak (ADP) to the strong (apo) RNA binding state. Using smFRET labels on the RNA to probe substrate binding and unwinding, we demonstrate that Pfa1(gp) enables Prp43(ADP) to switch between RNA-bound and RNA-unbound states instead of dissociating from the RNA. ATP binding to the apo-enzyme induces the translocation along the RNA, generating the unwinding force required to melt proximal RNA structures. During ATP turnover, Pfa1(gp) stimulates alternating of the RecA domains between open and closed states. Consequently, the translocation becomes faster than dissociation from the substrate in the ADP state, allowing processive movement along the RNA. We provide a mechanistic model of DEAH/RHA helicase motility and reveal the principles of Prp43 regulation by G-patch proteins."],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft 501100001659"],["dc.identifier.doi","10.1073/pnas.2203567119"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/118063"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.eissn","1091-6490"],["dc.relation.issn","0027-8424"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Regulation of the DEAH/RHA helicase Prp43 by the G-patch factor Pfa1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Poulis, Panagiotis"],["dc.contributor.author","Patel, Anoshi"],["dc.contributor.author","Rodnina, Marina V."],["dc.contributor.author","Adio, Sarah"],["dc.date.accessioned","2022-09-01T09:50:01Z"],["dc.date.available","2022-09-01T09:50:01Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n When reading consecutive mRNA codons, ribosomes move by exactly one triplet at a time to synthesize a correct protein. Some mRNA tracks, called slippery sequences, are prone to ribosomal frameshifting, because the same tRNA can read both 0- and –1-frame codon. Using smFRET we show that during EF-G-catalyzed translocation on slippery sequences a fraction of ribosomes spontaneously switches from rapid, accurate translation to a slow, frameshifting-prone translocation mode where the movements of peptidyl- and deacylated tRNA become uncoupled. While deacylated tRNA translocates rapidly, pept-tRNA continues to fluctuate between chimeric and posttranslocation states, which slows down the re-locking of the small ribosomal subunit head domain. After rapid release of deacylated tRNA, pept-tRNA gains unconstrained access to the –1-frame triplet, resulting in slippage followed by recruitment of the –1-frame aa-tRNA into the A site. Our data show how altered choreography of tRNA and ribosome movements reduces the translation fidelity of ribosomes translocating in a slow mode."],["dc.identifier.doi","10.1038/s41467-022-31852-w"],["dc.identifier.pii","31852"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113603"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","2041-1723"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Altered tRNA dynamics during translocation on slippery mRNA as determinant of spontaneous ribosome frameshifting"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5282"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","5298"],["dc.bibliographiccitation.volume","50"],["dc.contributor.author","Yi, Sung-Hui"],["dc.contributor.author","Petrychenko, Valentyn"],["dc.contributor.author","Schliep, Jan Erik"],["dc.contributor.author","Goyal, Akanksha"],["dc.contributor.author","Linden, Andreas"],["dc.contributor.author","Chari, Ashwin"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Stark, Holger"],["dc.contributor.author","Rodnina, Marina V"],["dc.contributor.author","Adio, Sarah"],["dc.contributor.author","Fischer, Niels"],["dc.date.accessioned","2022-06-01T09:39:22Z"],["dc.date.available","2022-06-01T09:39:22Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract Selection of the translation start codon is a key step during protein synthesis in human cells. We obtained cryo-EM structures of human 48S initiation complexes and characterized the intermediates of codon recognition by kinetic methods using eIF1A as a reporter. Both approaches capture two distinct ribosome populations formed on an mRNA with a cognate AUG codon in the presence of eIF1, eIF1A, eIF2–GTP–Met-tRNAiMet and eIF3. The ‘open’ 40S subunit conformation differs from the human 48S scanning complex and represents an intermediate preceding the codon recognition step. The ‘closed’ form is similar to reported structures of complexes from yeast and mammals formed upon codon recognition, except for the orientation of eIF1A, which is unique in our structure. Kinetic experiments show how various initiation factors mediate the population distribution of open and closed conformations until 60S subunit docking. Our results provide insights into the timing and structure of human translation initiation intermediates and suggest the differences in the mechanisms of start codon selection between mammals and yeast."],["dc.identifier.doi","10.1093/nar/gkac283"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/108454"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-572"],["dc.relation.eissn","1362-4962"],["dc.relation.issn","0305-1048"],["dc.title","Conformational rearrangements upon start codon recognition in human 48S translation initiation complex"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","258a"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","104"],["dc.contributor.author","Adio, Sarah"],["dc.contributor.author","Senyushkina, Tamara"],["dc.contributor.author","Wintermeyer, Wolfgang"],["dc.contributor.author","Rodnina, Marina"],["dc.date.accessioned","2022-03-01T11:44:56Z"],["dc.date.available","2022-03-01T11:44:56Z"],["dc.date.issued","2013"],["dc.identifier.doi","10.1016/j.bpj.2012.11.1448"],["dc.identifier.pii","S000634951202694X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103166"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0006-3495"],["dc.title","Translocation of tRNAs through the Ribosome followed by Single Molecule FRET"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","423"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Nature Structural & Molecular Biology"],["dc.bibliographiccitation.lastpage","428"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Bieling, P."],["dc.contributor.author","Beringer, Malte"],["dc.contributor.author","Adio, Sarah"],["dc.contributor.author","Rodnina, Marina"],["dc.date.accessioned","2017-09-07T11:53:05Z"],["dc.date.available","2017-09-07T11:53:05Z"],["dc.date.issued","2006"],["dc.description.abstract","Ribosomes catalyze the formation of peptide bonds between aminoacyl esters of transfer RNAs within a catalytic center composed of ribosomal RNA only. Here we show that the reaction of P-site formylmethionine ( fMet)-tRNA(fMet) with a modified A-site tRNA substrate, Phelac-tRNA(Phe), in which the nucleophilic amino group is replaced with a hydroxyl group, does not show the pH dependence observed with small substrate analogs such as puromycin and hydroxypuromycin. This indicates that acid-base catalysis by ribosomal residues is not important in the reaction with the full-size substrate. Rather, the ribosome catalyzes peptide bond formation by positioning the tRNAs, or their 3' termini, through interactions with rRNA that induce and/or stabilize a pH-insensitive conformation of the active site and provide a preorganized environment facilitating the reaction. The rate of peptide bond formation with unmodified Phe-tRNA(Phe) is estimated to be > 300 s(-1)."],["dc.identifier.doi","10.1038/nsmb1091"],["dc.identifier.gro","3143699"],["dc.identifier.isi","000237359700016"],["dc.identifier.pmid","16648860"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1242"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1545-9985"],["dc.title","Peptide bond formation does not involve acid-base catalysis by ribosomal residues"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Adio, Sarah"],["dc.contributor.author","Sharma, Heena"],["dc.contributor.author","Senyushkina, Tamara"],["dc.contributor.author","Karki, Prajwal"],["dc.contributor.author","Maracci, Cristina"],["dc.contributor.author","Wohlgemuth, Ingo"],["dc.contributor.author","Holtkamp, Wolf"],["dc.contributor.author","Peske, Frank"],["dc.contributor.author","Rodnina, Marina V."],["dc.date.accessioned","2019-07-25T11:30:31Z"],["dc.date.available","2019-07-25T11:30:31Z"],["dc.date.issued","2018"],["dc.description.abstract","Release factors RF1 and RF2 promote hydrolysis of peptidyl-tRNA during translation termination. The GTPase RF3 promotes recycling of RF1 and RF2. Using single molecule FRET and biochemical assays, we show that ribosome termination complexes that carry two factors, RF1-RF3 or RF2-RF3, are dynamic and fluctuate between non-rotated and rotated states, whereas each factor alone has its distinct signature on ribosome dynamics and conformation. Dissociation of RF1 depends on peptide release and the presence of RF3, whereas RF2 can dissociate spontaneously. RF3 binds in the GTP-bound state and can rapidly dissociate without GTP hydrolysis from termination complex carrying RF1. In the absence of RF1, RF3 is stalled on ribosomes if GTP hydrolysis is blocked. Our data suggest how the assembly of the ribosome-RF1-RF3-GTP complex, peptide release, and ribosome fluctuations promote termination of protein synthesis and recycling of the release factors."],["dc.identifier.doi","10.7554/eLife.34252"],["dc.identifier.pmid","29889659"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62052"],["dc.language.iso","en"],["dc.relation.eissn","2050-084X"],["dc.relation.issn","2050-084X"],["dc.title","Dynamics of ribosomes and release factors during translation termination in E. coli"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2187"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.lastpage","2196"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Sharma, Heena"],["dc.contributor.author","Adio, Sarah"],["dc.contributor.author","Senyushkina, Tamara"],["dc.contributor.author","Belardinelli, Riccardo"],["dc.contributor.author","Peske, Frank"],["dc.contributor.author","Rodnina, Marina V."],["dc.date.accessioned","2017-09-07T11:44:43Z"],["dc.date.available","2017-09-07T11:44:43Z"],["dc.date.issued","2016"],["dc.description.abstract","Ribosome dynamics play an important role in translation. The rotation of the ribosomal subunits relative to one another is essential for tRNA-mRNA translocation. An important unresolved question is whether subunit rotation limits the rate of translocation. Here, we monitor subunit rotation relative to peptide bond formation and translocation using ensemble kinetics and single-molecule FRET. We observe that spontaneous forward subunit rotation occurs at a rate of 40 s(-1), independent of the rate of preceding peptide bond formation. Elongation factor G (EF-G) accelerates forward subunit rotation to 200 s(-1). tRNA-mRNA movement is much slower (10-40 s(-1)), suggesting that forward subunit rotation does not limit the rate of translocation. The transition back to the non-rotated state of the ribosome kinetically coincides with tRNA-mRNA movement. Thus, largescale movements of the ribosome are intrinsically rapid and gated by its ligands such as EF-G and tRNA."],["dc.identifier.doi","10.1016/j.celrep.2016.07.051"],["dc.identifier.gro","3141633"],["dc.identifier.isi","000382310100015"],["dc.identifier.pmid","27524615"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3456"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft [Sonderforschungsbereich 860]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","2211-1247"],["dc.title","Kinetics of Spontaneous and EF-G-Accelerated Rotation of Ribosomal Subunits"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]