Structural characterization of eukaryotic mRNA decay factors involved in post-transcriptional gene regulation

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dc.contributor.advisor Stehle, Thilo (Prof. Dr.) Boland, Andreas 2014-09-18T09:01:36Z 2014-09-18T09:01:36Z 2014
dc.identifier.other 414643143 de_DE
dc.identifier.uri de_DE
dc.description.abstract In animal cells, miRNAs silence the expression of mRNA targets through translational repression and/or deadenylation. Silencing requires the association of miRNAs to an Argonaute protein, which moreover binds to a member of the GW182/TNRC6C protein family. In turn, GW182 proteins interact with the two major cytoplasmic deadenylase complexes, the PAN2-PAN3 complex and the CCR4-NOT complex, to induce deadenylation and hence promote decay of miRNA targets. Structural insights into the assembly of the CCR4-NOT and PAN2-PAN3 complexes could be obtained by determining several sub-complexes of these multi-subunit deadenylases, including the crystal structures of the NOT1-CAF40 complex, the minimal NOT module (composed of the C-terminal domains of NOT1, NOT2 and NOT3) and the crystal structure of the folded domains of the PAN3 adaptor protein. Nevertheless, the most remarkable features were the identification of tryptophan-binding pockets in CAF40/CNOT9 and PAN3, providing a rational basis for the recruitment of the deadenylases to miRNA targets through GW182/TNRC6 proteins. Finally, the first crystal structure of the MID-PIWI lobe from a eukaryotic Argonaute protein was solved, which provided first molecular insights into eukaryotic Argonaute biology. en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podok de_DE
dc.rights.uri de_DE
dc.rights.uri en
dc.subject.classification RNS , Abbau de_DE
dc.subject.ddc 500 de_DE
dc.subject.ddc 570 de_DE
dc.subject.other mRNA decay en
dc.subject.other silecing en
dc.subject.other deadenylation en
dc.subject.other miRNA en
dc.subject.other CCR4-NOT en
dc.subject.other PAN2-PAN3 en
dc.title Structural characterization of eukaryotic mRNA decay factors involved in post-transcriptional gene regulation en
dc.type Dissertation de_DE
dcterms.dateAccepted 2014-06-25
utue.publikation.fachbereich Biochemie de_DE
utue.publikation.fakultaet 7 Mathematisch-Naturwissenschaftliche Fakultät de_DE


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