Mühlhausen, Stefanie

[["dc.bibliographiccitation.artnumber","258"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Biology"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Mühlhausen, Stefanie"],["dc.contributor.author","Plessmann, Uwe"],["dc.contributor.author","Mienkus, Peter"],["dc.contributor.author","Sternisek, Pia"],["dc.contributor.author","Perl, Thorsten"],["dc.contributor.author","Weig, Michael"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Bader, Oliver"],["dc.contributor.author","Kollmar, Martin"],["dc.contributor.author","Schmitt, Hans Dieter"],["dc.date.accessioned","2022-01-11T14:06:08Z"],["dc.date.accessioned","2022-08-18T12:34:34Z"],["dc.date.available","2022-01-11T14:06:08Z"],["dc.date.available","2022-08-18T12:34:34Z"],["dc.date.issued","2021-12-04"],["dc.date.updated","2022-07-29T12:07:10Z"],["dc.description.abstract","Abstract\r\n \r\n Background\r\n Yeasts of the CTG-clade lineage, which includes the human-infecting Candida albicans, Candida parapsilosis and Candida tropicalis species, are characterized by an altered genetic code. Instead of translating CUG codons as leucine, as happens in most eukaryotes, these yeasts, whose ancestors are thought to have lost the relevant leucine-tRNA gene, translate CUG codons as serine using a serine-tRNA with a mutated anticodon, \r\n \r\n \r\n \r\n \r\n \r\n tRNA\r\n CAG\r\n Ser\r\n \r\n \r\n $ {\\mathrm{tRNA}}_{\\mathrm{CAG}}^{\\mathrm{Ser}} $\r\n . Previously reported experiments have suggested that 3–5% of the CTG-clade CUG codons are mistranslated as leucine due to mischarging of the \r\n \r\n \r\n \r\n \r\n \r\n tRNA\r\n CAG\r\n Ser\r\n \r\n \r\n $ {\\mathrm{tRNA}}_{\\mathrm{CAG}}^{\\mathrm{Ser}} $\r\n . The mistranslation was suggested to result in variable surface proteins explaining fast host adaptation and pathogenicity.\r\n \r\n \r\n Results\r\n In this study, we reassess this potential mistranslation by high-resolution mass spectrometry-based proteogenomics of multiple CTG-clade yeasts, including various C. albicans strains, isolated from colonized and from infected human body sites, and C. albicans grown in yeast and hyphal forms. Our data do not support a bias towards CUG codon mistranslation as leucine. Instead, our data suggest that (i) CUG codons are mistranslated at a frequency corresponding to the normal extent of ribosomal mistranslation with no preference for specific amino acids, (ii) CUG codons are as unambiguous (or ambiguous) as the related CUU leucine and UCC serine codons, (iii) tRNA anticodon loop variation across the CTG-clade yeasts does not result in any difference of the mistranslation level, and (iv) CUG codon unambiguity is independent of C. albicans’ strain pathogenicity or growth form.\r\n \r\n \r\n Conclusions\r\n Our findings imply that C. albicans does not decode CUG ambiguously. This suggests that the proposed misleucylation of the \r\n \r\n \r\n \r\n \r\n \r\n tRNA\r\n CAG\r\n Ser\r\n \r\n \r\n $ {\\mathrm{tRNA}}_{\\mathrm{CAG}}^{\\mathrm{Ser}} $\r\n might be as prevalent as every other misacylation or mistranslation event and, if at all, be just one of many reasons causing phenotypic diversity."],["dc.identifier.citation","BMC Biology. 2021 Dec 04;19(1):258"],["dc.identifier.doi","10.1186/s12915-021-01197-9"],["dc.identifier.pii","1197"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97834"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112931"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.publisher","BioMed Central"],["dc.relation.eissn","1741-7007"],["dc.rights.holder","The Author(s)"],["dc.subject","Proteogenomics"],["dc.subject","Pathogen"],["dc.subject","Candida albicans"],["dc.subject","Genetic code"],["dc.title","Proteogenomics analysis of CUG codon translation in the human pathogen Candida albicans"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2046-2057.e5"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Current biology : CB"],["dc.bibliographiccitation.lastpage","2057.e5"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Mühlhausen, Stefanie"],["dc.contributor.author","Schmitt, Hans Dieter"],["dc.contributor.author","Pan, Kuan-Ting"],["dc.contributor.author","Plessmann, Uwe"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Hurst, Laurence D"],["dc.contributor.author","Kollmar, Martin"],["dc.date.accessioned","2018-11-28T09:07:20Z"],["dc.date.available","2018-11-28T09:07:20Z"],["dc.date.issued","2018-07-09"],["dc.description.abstract","Although the \"universal\" genetic code is now known not to be universal, and stop codons can have multiple meanings, one regularity remains, namely that for a given sense codon there is a unique translation. Examining CUG usage in yeasts that have transferred CUG away from leucine, we here report the first example of dual coding: Ascoidea asiatica stochastically encodes CUG as both serine and leucine in approximately equal proportions. This is deleterious, as evidenced by CUG codons being rare, never at conserved serine or leucine residues, and predominantly in lowly expressed genes. Related yeasts solve the problem by loss of function of one of the two tRNAs. This dual coding is consistent with the tRNA-loss-driven codon reassignment hypothesis, and provides a unique example of a proteome that cannot be deterministically predicted. VIDEO ABSTRACT."],["dc.identifier.doi","10.1016/j.cub.2018.04.085"],["dc.identifier.pmid","29910077"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56968"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.relation.eissn","1879-0445"],["dc.title","Endogenous Stochastic Decoding of the CUG Codon by Competing Ser- and Leu-tRNAs in Ascoidea asiatica"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","945-55"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Genome research"],["dc.bibliographiccitation.lastpage","955"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Mühlhausen, Stefanie"],["dc.contributor.author","Findeisen, Peggy"],["dc.contributor.author","Plessmann, Uwe"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Kollmar, Martin"],["dc.date.accessioned","2018-11-28T09:31:29Z"],["dc.date.available","2018-11-28T09:31:29Z"],["dc.date.issued","2016"],["dc.description.abstract","The genetic code is the cellular translation table for the conversion of nucleotide sequences into amino acid sequences. Changes to the meaning of sense codons would introduce errors into almost every translated message and are expected to be highly detrimental. However, reassignment of single or multiple codons in mitochondria and nuclear genomes, although extremely rare, demonstrates that the code can evolve. Several models for the mechanism of alteration of nuclear genetic codes have been proposed (including \"codon capture,\" \"genome streamlining,\" and \"ambiguous intermediate\" theories), but with little resolution. Here, we report a novel sense codon reassignment in Pachysolen tannophilus, a yeast related to the Pichiaceae. By generating proteomics data and using tRNA sequence comparisons, we show that Pachysolen translates CUG codons as alanine and not as the more usual leucine. The Pachysolen tRNACAG is an anticodon-mutated tRNA(Ala) containing all major alanine tRNA recognition sites. The polyphyly of the CUG-decoding tRNAs in yeasts is best explained by a tRNA loss driven codon reassignment mechanism. Loss of the CUG-tRNA in the ancient yeast is followed by gradual decrease of respective codons and subsequent codon capture by tRNAs whose anticodon is not part of the aminoacyl-tRNA synthetase recognition region. Our hypothesis applies to all nuclear genetic code alterations and provides several testable predictions. We anticipate more codon reassignments to be uncovered in existing and upcoming genome projects."],["dc.identifier.doi","10.1101/gr.200931.115"],["dc.identifier.pmid","27197221"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56973"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.relation.eissn","1549-5469"],["dc.title","A novel nuclear genetic code alteration in yeasts and the evolution of codon reassignment in eukaryotes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]