Krebber, Heike

[["dc.bibliographiccitation.firstpage","3199"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.lastpage","3214.e3"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Becker, Daniel"],["dc.contributor.author","Hirsch, Anna Greta"],["dc.contributor.author","Bender, Lysann"],["dc.contributor.author","Lingner, Thomas"],["dc.contributor.author","Salinas, Gabriela"],["dc.contributor.author","Krebber, Heike"],["dc.date.accessioned","2020-12-10T14:23:02Z"],["dc.date.available","2020-12-10T14:23:02Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.celrep.2019.05.031"],["dc.identifier.issn","2211-1247"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16442"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71808"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Nuclear Pre-snRNA Export Is an Essential Quality Assurance Mechanism for Functional Spliceosomes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0149571"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Neumann, Bettina"],["dc.contributor.author","Wu, Haijia"],["dc.contributor.author","Hackmann, Alexandra"],["dc.contributor.author","Krebber, Heike"],["dc.date.accessioned","2018-11-07T10:18:14Z"],["dc.date.available","2018-11-07T10:18:14Z"],["dc.date.issued","2016"],["dc.description.abstract","The DEAD-box RNA-helicase Dbp5/Rat8 is known for its function in nuclear mRNA export, where it displaces the export receptor Mex67 from the mRNA at the cytoplasmic side of the nuclear pore complex (NPC). Here we show that Dbp5 is also required for the nuclear export of both pre-ribosomal subunits. Yeast temperature-sensitive dbp5 mutants accumulate both ribosomal particles in their nuclei. Furthermore, Dbp5 genetically and physically interacts with known ribosomal transport factors such as Nmd3. Similar to mRNA export we show that also for ribosomal transport Dbp5 is required at the cytoplasmic side of the NPC. However, unlike its role in mRNA export, Dbp5 does not seem to undergo its ATPase cycle for this function, as ATPase-deficient dbp5 mutants that selectively inhibit mRNA export do not affect ribosomal transport. Furthermore, mutants of GLE1, the ATPase stimulating factor of Dbp5, show no major ribosomal export defects. Consequently, while Dbp5 uses its ATPase cycle to displace the export receptor Mex67 from the translocated mRNAs, Mex67 remains bound to ribosomal subunits upon transit to the cytoplasm, where it is detectable on translating ribosomes. Therefore, we propose a model, in which Dbp5 supports ribosomal transport by capturing ribosomal subunits upon their cytoplasmic appearance at the NPC, possibly by binding export factors such as Mex67. Thus, our findings reveal that although different ribonucleoparticles, mRNAs and pre-ribosomal subunits, use shared export factors, they utilize different transport mechanisms."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [SFB860]"],["dc.identifier.doi","10.1371/journal.pone.0149571"],["dc.identifier.isi","000370054100165"],["dc.identifier.pmid","26872259"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12933"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41395"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Nuclear Export of Pre-Ribosomal Subunits Requires Dbp5, but Not as an RNA-Helicase as for mRNA Export"],["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","1630"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.lastpage","1638"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Wu, Haijia"],["dc.contributor.author","Becker, Daniel"],["dc.contributor.author","Krebber, Heike"],["dc.date.accessioned","2018-11-07T09:35:03Z"],["dc.date.available","2018-11-07T09:35:03Z"],["dc.date.issued","2014"],["dc.description.abstract","Telomerases protect the ends of linear chromosomes from shortening. They are composed of an RNA (TLC1 in S. cerevisiae) and several proteins. TLC1 undergoes several maturation steps before it is exported into the cytoplasm to recruit the Est proteins for complete assembly. The mature telomerase is subsequently reimported into the nucleus, where it fulfills its function on telomeres. Here, we show that TLC1 export into the cytoplasm requires not only the Ran GTPase-dependent karyopherin Crm1/Xpo1 but also the mRNA export machinery. mRNA export factor mutants accumulate mature and export-competent TLC1 RNAs in their nuclei. Moreover, TLC1 physically interacts with the mRNA transport factors Mex67 and Dbp5/Rat8. Most importantly, we show that the nuclear export of TLC1 is an essential step for the formation of the functional RNA containing enzyme, because blocking TLC1 export in the mex67-5 xpo1-1 double mutant prevents its cytoplasmic maturation and leads to telomere shortening."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft (DFG); [SFB 860]"],["dc.identifier.doi","10.1016/j.celrep.2014.08.021"],["dc.identifier.isi","000343867400004"],["dc.identifier.pmid","25220466"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11359"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32308"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.relation.issn","2211-1247"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","Telomerase RNA TLC1 Shuttling to the Cytoplasm Requires mRNA Export Factors and Is Important for Telomere Maintenance"],["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.artnumber","UNSP e63745"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Karpiuk, Oleksandra"],["dc.contributor.author","Tieg, Bettina"],["dc.contributor.author","Kriegs, Malte"],["dc.contributor.author","Dikomey, Ekkehard"],["dc.contributor.author","Krebber, Heike"],["dc.contributor.author","Begus-Nahrmann, Yvonne"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2018-11-07T09:24:36Z"],["dc.date.available","2018-11-07T09:24:36Z"],["dc.date.issued","2013"],["dc.description.abstract","Unlike other metazoan mRNAs, replication-dependent histone gene transcripts are not polyadenylated but instead have a conserved stem-loop structure at their 39 end. Our previous work has shown that under certain conditions replication-dependent histone genes can produce alternative transcripts that are polyadenylated at the 39 end and, in some cases, spliced. A number of microarray studies examining the expression of polyadenylated mRNAs identified changes in the levels of histone transcripts e. g. during differentiation and tumorigenesis. However, it remains unknown which histone genes produce polyadenylated transcripts and which conditions regulate this process. In the present study we examined the expression and polyadenylation of the human histone H2B gene complement in various cell lines. We demonstrate that H2B genes display a distinct expression pattern that is varies between different cell lines. Further we show that the fraction of polyadenylated HIST1H2BD and HIST1H2AC transcripts is increased during differentiation of human mesenchymal stem cells (hMSCs) and human fetal osteoblast (hFOB 1.19). Furthermore, we observed an increased fraction of polyadenylated transcripts produced from the histone genes in cells following ionizing radiation. Finally, we show that polyadenylated transcripts are transported to the cytoplasm and found on polyribosomes. Thus, we propose that the production of polyadenylated histone mRNAs from replication-dependent histone genes is a regulated process induced under specific cellular circumstances."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2013"],["dc.identifier.doi","10.1371/journal.pone.0063745"],["dc.identifier.isi","000320362700053"],["dc.identifier.pmid","23717473"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9111"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29865"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","A Subset of Histone H2B Genes Produces Polyadenylated mRNAs under a Variety of Cellular Conditions"],["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","e3000423"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Frumkin, Idan"],["dc.contributor.author","Yofe, Ido"],["dc.contributor.author","Bar-Ziv, Raz"],["dc.contributor.author","Gurvich, Yonat"],["dc.contributor.author","Lu, Yen-Yun"],["dc.contributor.author","Voichek, Yoav"],["dc.contributor.author","Towers, Ruth"],["dc.contributor.author","Schirman, Dvir"],["dc.contributor.author","Krebber, Heike"],["dc.contributor.author","Pilpel, Yitzhak"],["dc.contributor.editor","Hurst, Laurence D."],["dc.date.accessioned","2020-12-10T18:42:04Z"],["dc.date.available","2020-12-10T18:42:04Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1371/journal.pbio.3000423"],["dc.identifier.eissn","1545-7885"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16463"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77791"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Evolution of intron splicing towards optimized gene expression is based on various Cis- and Trans-molecular mechanisms"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1085"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Beißel, Christian"],["dc.contributor.author","Grosse, Sebastian"],["dc.contributor.author","Krebber, Heike"],["dc.date.accessioned","2020-12-10T18:47:10Z"],["dc.date.available","2020-12-10T18:47:10Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.3390/ijms21031085"],["dc.identifier.eissn","1422-0067"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17332"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78666"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Dbp5/DDX19 between Translational Readthrough and Nonsense Mediated Decay"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","22174"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Hirsch, Anna Greta"],["dc.contributor.author","Becker, Daniel"],["dc.contributor.author","Lamping, Jan-Philipp"],["dc.contributor.author","Krebber, Heike"],["dc.date.accessioned","2021-12-01T09:23:04Z"],["dc.date.available","2021-12-01T09:23:04Z"],["dc.date.issued","2021"],["dc.description.abstract","Telomerases elongate the ends of chromosomes required for cell immortality through their reverse transcriptase activity. By using the model organism Saccharomyces cerevisiae we defined the order in which the holoenzyme matures. First, a longer precursor of the telomerase RNA, TLC1 is transcribed and exported into the cytoplasm, where it associates with the protecting Sm-ring, the Est and the Pop proteins. This partly matured telomerase is re-imported into the nucleus via Mtr10 and a novel TLC1 -import factor, the karyopherin Cse1. Remarkably, while mutations in all known transport factors result in short telomere ends, mutation in CSE1 leads to the amplification of Y′ elements in the terminal chromosome regions and thus elongated telomere ends. Cse1 does not only support TLC1 import, but also the Sm-ring stabilization on the RNA enableling Mtr10 contact and nuclear import. Thus, Sm-ring formation and import factor contact resembles a quality control step in the maturation process of the telomerase. The re-imported immature TLC1 is finally trimmed into the 1158 nucleotides long mature form via the nuclear exosome. TMG-capping of TLC1 finalizes maturation, leading to mature telomerase."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.1038/s41598-021-01599-3"],["dc.identifier.pii","1599"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94552"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation.eissn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.title","Unraveling the stepwise maturation of the yeast telomerase including a Cse1 and Mtr10 mediated quality control checkpoint"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4798"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","4813"],["dc.bibliographiccitation.volume","47"],["dc.contributor.author","Beissel, Christian"],["dc.contributor.author","Neumann, Bettina"],["dc.contributor.author","Uhse, Simon"],["dc.contributor.author","Hampe, Irene"],["dc.contributor.author","Karki, Prajwal"],["dc.contributor.author","Krebber, Heike"],["dc.date.accessioned","2019-07-25T10:31:21Z"],["dc.date.available","2019-07-25T10:31:21Z"],["dc.date.issued","2019"],["dc.description.abstract","Translation termination requires eRF1 and eRF3 for polypeptide- and tRNA-release on stop codons. Additionally, Dbp5/DDX19 and Rli1/ABCE1 are required; however, their function in this process is currently unknown. Using a combination of in vivo and in vitro experiments, we show that they regulate a stepwise assembly of the termination complex. Rli1 and eRF3-GDP associate with the ribosome first. Subsequently, Dbp5-ATP delivers eRF1 to the stop codon and in this way prevents a premature access of eRF3. Dbp5 dissociates upon placing eRF1 through ATP-hydrolysis. This in turn enables eRF1 to contact eRF3, as the binding of Dbp5 and eRF3 to eRF1 is mutually exclusive. Defects in the Dbp5-guided eRF1 delivery lead to premature contact and premature dissociation of eRF1 and eRF3 from the ribosome and to subsequent stop codon readthrough. Thus, the stepwise Dbp5-controlled termination complex assembly is essential for regular translation termination events. Our data furthermore suggest a possible role of Dbp5/DDX19 in alternative translation termination events, such as during stress response or in developmental processes, which classifies the helicase as a potential drug target for nonsense suppression therapy to treat cancer and neurodegenerative diseases."],["dc.identifier.doi","10.1093/nar/gkz177"],["dc.identifier.pmid","30873535"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16303"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62049"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1362-4962"],["dc.relation.issn","0305-1048"],["dc.relation.issn","1362-4962"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Translation termination depends on the sequential ribosomal entry of eRF1 and eRF3"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","11275"],["dc.bibliographiccitation.issue","20"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Lu, Yen-Yun"],["dc.contributor.author","Krebber, Heike"],["dc.date.accessioned","2021-12-01T09:22:50Z"],["dc.date.available","2021-12-01T09:22:50Z"],["dc.date.issued","2021"],["dc.date.updated","2022-09-03T18:54:25Z"],["dc.description.abstract","Pre-mRNA splicing is critical for cells, as defects in this process can lead to altered open reading frames and defective proteins, potentially causing neurodegenerative diseases and cancer. Introns are removed in the nucleus and splicing is documented by the addition of exon-junction-complexes (EJCs) at exon-exon boundaries. This “memory” of splicing events is important for the ribosome, which translates the RNAs in the cytoplasm. In case a stop codon was detected before an EJC, translation is blocked and the RNA is eliminated by the nonsense-mediated decay (NMD). In the model organism Saccharomyces cerevisiae, two guard proteins, Gbp2 and Hrb1, have been identified as nuclear quality control factors for splicing. In their absence, intron-containing mRNAs leak into the cytoplasm. Their presence retains transcripts until the process is completed and they release the mRNAs by recruitment of the export factor Mex67. On transcripts that experience splicing problems, these guard proteins recruit the nuclear RNA degradation machinery. Interestingly, they continue their quality control function on exported transcripts. They support NMD by inhibiting translation and recruiting the cytoplasmic degradation factors. In this way, they link the nuclear and cytoplasmic quality control systems. These discoveries are also intriguing for humans, as homologues of these guard proteins are present also in multicellular organisms. Here, we provide an overview of the quality control mechanisms of pre-mRNA splicing, and present Gbp2 and Hrb1, as well as their human counterparts, as important players in these pathways."],["dc.description.abstract","Pre-mRNA splicing is critical for cells, as defects in this process can lead to altered open reading frames and defective proteins, potentially causing neurodegenerative diseases and cancer. Introns are removed in the nucleus and splicing is documented by the addition of exon-junction-complexes (EJCs) at exon-exon boundaries. This “memory” of splicing events is important for the ribosome, which translates the RNAs in the cytoplasm. In case a stop codon was detected before an EJC, translation is blocked and the RNA is eliminated by the nonsense-mediated decay (NMD). In the model organism Saccharomyces cerevisiae, two guard proteins, Gbp2 and Hrb1, have been identified as nuclear quality control factors for splicing. In their absence, intron-containing mRNAs leak into the cytoplasm. Their presence retains transcripts until the process is completed and they release the mRNAs by recruitment of the export factor Mex67. On transcripts that experience splicing problems, these guard proteins recruit the nuclear RNA degradation machinery. Interestingly, they continue their quality control function on exported transcripts. They support NMD by inhibiting translation and recruiting the cytoplasmic degradation factors. In this way, they link the nuclear and cytoplasmic quality control systems. These discoveries are also intriguing for humans, as homologues of these guard proteins are present also in multicellular organisms. Here, we provide an overview of the quality control mechanisms of pre-mRNA splicing, and present Gbp2 and Hrb1, as well as their human counterparts, as important players in these pathways."],["dc.identifier.doi","10.3390/ijms222011275"],["dc.identifier.pii","ijms222011275"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94493"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation.eissn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Nuclear mRNA Quality Control and Cytoplasmic NMD Are Linked by the Guard Proteins Gbp2 and Hrb1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]