Karki, Prajwal

[["dc.bibliographiccitation.firstpage","752"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Nature Structural & Molecular Biology"],["dc.bibliographiccitation.lastpage","757"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Florin, Tanja"],["dc.contributor.author","Maracci, Cristina"],["dc.contributor.author","Graf, Michael"],["dc.contributor.author","Karki, Prajwal"],["dc.contributor.author","Klepacki, Dorota"],["dc.contributor.author","Berninghausen, Otto"],["dc.contributor.author","Beckmann, Roland"],["dc.contributor.author","Vázquez-Laslop, Nora"],["dc.contributor.author","Wilson, Daniel N."],["dc.contributor.author","Rodnina, Marina V."],["dc.contributor.author","Mankin, Alexander S."],["dc.date.accessioned","2018-01-24T13:03:20Z"],["dc.date.available","2018-01-24T13:03:20Z"],["dc.date.issued","2017"],["dc.description.abstract","Many antibiotics stop bacterial growth by inhibiting different steps of protein synthesis. However, no specific inhibitors of translation termination are known. Proline-rich antimicrobial peptides, a component of the antibacterial defense system of multicellular organisms, interfere with bacterial growth by inhibiting translation. Here we show that Api137, a derivative of the insect-produced antimicrobial peptide apidaecin, arrests terminating ribosomes using a unique mechanism of action. Api137 binds to the Escherichia coli ribosome and traps release factor (RF) RF1 or RF2 subsequent to the release of the nascent polypeptide chain. A high-resolution cryo-EM structure of the ribosome complexed with RF1 and Api137 reveals the molecular interactions that lead to RF trapping. Api137-mediated depletion of the cellular pool of free release factors causes the majority of ribosomes to stall at stop codons before polypeptide release, thereby resulting in a global shutdown of translation termination."],["dc.identifier.doi","10.1038/nsmb.3439"],["dc.identifier.pmid","28741611"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11795"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1545-9985"],["dc.title","An antimicrobial peptide that inhibits translation by trapping release factors on the ribosome"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.contributor.author","Karki, Prajwal"],["dc.contributor.author","Carney, Travis D"],["dc.contributor.author","Maracci, Cristina"],["dc.contributor.author","Yatsenko, Andriy S"],["dc.contributor.author","Shcherbata, Halyna R"],["dc.contributor.author","Rodnina, Marina V."],["dc.date.accessioned","2022-01-11T14:08:08Z"],["dc.date.available","2022-01-11T14:08:08Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Translational readthrough (TR) occurs when the ribosome decodes a stop codon as a sense codon, resulting in two protein isoforms synthesized from the same mRNA. TR has been identified in several eukaryotic organisms; however, its biological significance and mechanism remain unclear. Here, we quantify TR of several candidate genes in Drosophila melanogaster and characterize the regulation of TR in the large Maf transcription factor Traffic jam (Tj). Using CRISPR/Cas9-generated mutant flies, we show that the TR-generated Tj isoform is expressed in a subset of neural cells of the central nervous system and is excluded from the somatic cells of gonads. Control of TR in Tj is critical for preservation of neuronal integrity and maintenance of reproductive health. The tissue-specific distribution of a release factor splice variant, eRF1H, plays a critical role in modulating differential TR of leaky stop codon contexts. Fine-tuning of gene regulatory functions of transcription factors by TR provides a potential mechanism for cell-specific regulation of gene expression."],["dc.description.abstract","Abstract Translational readthrough (TR) occurs when the ribosome decodes a stop codon as a sense codon, resulting in two protein isoforms synthesized from the same mRNA. TR has been identified in several eukaryotic organisms; however, its biological significance and mechanism remain unclear. Here, we quantify TR of several candidate genes in Drosophila melanogaster and characterize the regulation of TR in the large Maf transcription factor Traffic jam (Tj). Using CRISPR/Cas9-generated mutant flies, we show that the TR-generated Tj isoform is expressed in a subset of neural cells of the central nervous system and is excluded from the somatic cells of gonads. Control of TR in Tj is critical for preservation of neuronal integrity and maintenance of reproductive health. The tissue-specific distribution of a release factor splice variant, eRF1H, plays a critical role in modulating differential TR of leaky stop codon contexts. Fine-tuning of gene regulatory functions of transcription factors by TR provides a potential mechanism for cell-specific regulation of gene expression."],["dc.identifier.doi","10.1093/nar/gkab1189"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97941"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.relation.eissn","1362-4962"],["dc.relation.issn","0305-1048"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0/"],["dc.title","Tissue-specific regulation of translational readthrough tunes functions of the traffic jam transcription factor"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1056"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","1067"],["dc.bibliographiccitation.volume","48"],["dc.contributor.author","Rodnina, Marina V."],["dc.contributor.author","Korniy, Natalia"],["dc.contributor.author","Klimova, Mariia"],["dc.contributor.author","Karki, Prajwal"],["dc.contributor.author","Peng, Bee-Zen"],["dc.contributor.author","Senyushkina, Tamara"],["dc.contributor.author","Belardinelli, Riccardo"],["dc.contributor.author","Maracci, Cristina"],["dc.contributor.author","Wohlgemuth, Ingo"],["dc.contributor.author","Samatova, Ekaterina"],["dc.contributor.author","Peske, Frank"],["dc.date.accessioned","2022-03-01T11:46:50Z"],["dc.date.available","2022-03-01T11:46:50Z"],["dc.date.issued","2019"],["dc.description.abstract","Abstract During canonical translation, the ribosome moves along an mRNA from the start to the stop codon in exact steps of one codon at a time. The collinearity of the mRNA and the protein sequence is essential for the quality of the cellular proteome. Spontaneous errors in decoding or translocation are rare and result in a deficient protein. However, dedicated recoding signals in the mRNA can reprogram the ribosome to read the message in alternative ways. This review summarizes the recent advances in understanding the mechanisms of three types of recoding events: stop-codon readthrough, –1 ribosome frameshifting and translational bypassing. Recoding events provide insights into alternative modes of ribosome dynamics that are potentially applicable to other non-canonical modes of prokaryotic and eukaryotic translation."],["dc.description.abstract","Abstract During canonical translation, the ribosome moves along an mRNA from the start to the stop codon in exact steps of one codon at a time. The collinearity of the mRNA and the protein sequence is essential for the quality of the cellular proteome. Spontaneous errors in decoding or translocation are rare and result in a deficient protein. However, dedicated recoding signals in the mRNA can reprogram the ribosome to read the message in alternative ways. This review summarizes the recent advances in understanding the mechanisms of three types of recoding events: stop-codon readthrough, –1 ribosome frameshifting and translational bypassing. Recoding events provide insights into alternative modes of ribosome dynamics that are potentially applicable to other non-canonical modes of prokaryotic and eukaryotic translation."],["dc.identifier.doi","10.1093/nar/gkz783"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103816"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1362-4962"],["dc.relation.issn","0305-1048"],["dc.title","Translational recoding: canonical translation mechanisms reinterpreted"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["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"]]