| dc.contributor.advisor | Krebber, Heike Prof. Dr. | |
| dc.contributor.author | Zander, Gesa | |
| dc.date.accessioned | 2017-05-17T09:25:13Z | |
| dc.date.available | 2017-05-17T09:25:13Z | |
| dc.date.issued | 2017-05-17 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0023-3E4A-B | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-6298 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | Characterization of mRNA export and nuclear quality control under heat stress in the yeast Saccharomyces cerevisiae | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Krebber, Heike Prof. Dr. | |
| dc.date.examination | 2017-03-27 | |
| dc.description.abstracteng | Elevated temperatures and other changes of the environment a cell lives in, can have tremendous impact on cellular processes and integrity. To counteract these threats, cells have established various mechanisms to avoid severe damage and ensure survival. One of them is the highly-conserved heat shock response that results in expression of a special set of proteins among them chaperones, which aid denatured proteins in refolding and protect them from further destruction. This response to heat stress is accompanied by the disruption of normal cellular processes like general mRNA transcription, splicing and export in the nucleus and translation of housekeeping transcripts in the cytoplasm.
This study analyzed by what mechanisms the cell can distinguish between normal mRNAs that need to be blocked in the nucleus and stress responsive transcripts, which are required to be exported and translated. Several experiments show that while the normal mRNA export relies on the support of the shuttling adaptor proteins Npl3, Gbp2, Hrb1 and Nab2, a general dissociation of these proteins together with the export receptor Mex67 from mRNAs can be observed under stress, which explains the mRNA export block. Heat stress (HS) mRNAs in turn are exported by direct binding of Mex67 without the need of any known adaptor. This preferential binding of Mex67 to mRNAs expressed under heat stress is most likely facilitated through its early recruitment by the heat shock transcription factor Hsf1. Further experiments revealed that replacing the promoter of a normal mRNA with a stress responsive promoter and even artificially inserting an Hsf1 binding site can turn a housekeeping mRNA in a heat stress responsive transcript. All these mRNAs, strongly expressed under heat stress, strikingly bypass nuclear quality control and are quickly exported. Under normal conditions faulty mRNAs are labeled by the Mtr4-containing TRAMP complex and degraded by the nuclear Rrp6-containing exosome. Detection of errors in normal mRNAs is most likely coupled to the adaptor proteins, which might control correctness of every maturation step. As mRNA adaptor proteins are dispensable during HS mRNA transcription and export, this appears to be the mode of how heat stress transcripts evade to be quality controlled.
These mechanisms probably result in two different mRNA export ways: under normal conditions adaptor proteins facilitate a close quality control of an mRNA before Mex67 can associate and perform export, while upon heat stress direct binding by Mex67 results in a fast export of HS mRNAs that are not controlled for their quality. Thus, even though more faulty HS mRNA reach the cytoplasm, the fast response to stress appears to be more beneficial for survival. | de |
| dc.contributor.coReferee | Kehlenbach, Ralph Prof. Dr. | |
| dc.contributor.thirdReferee | Pöggeler, Stefanie Prof. Dr. | |
| dc.contributor.thirdReferee | Valerius, Oliver Dr. | |
| dc.contributor.thirdReferee | Ficner, Ralf Prof. Dr. | |
| dc.contributor.thirdReferee | Kramer, Wilfried PD Dr. | |
| dc.subject.eng | mRNA export | de |
| dc.subject.eng | quality control | de |
| dc.subject.eng | heat stress | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0023-3E4A-B-7 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 887658520 | |