The role of human and Drosophila NXF proteins in nuclear mRNA ...

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Eingereicht am: 18.02.2003 Mitglieder der Prüfungskommission: Vorsitzender: Prof. Dr. Rainer Hedrich 1. Gutachter: Prof. Dr. Ulrich Scheer 2. Gutachter: Dr. habil. Matthias Hentze Tag des Promotionskolloquiums: 28.05.2003 Doktorurkunde ausgehändigt am: ................................................
This thesis describes work carried out in the laboratory of Dr Elisa Izaurralde at the European Molecular Biology Laboratory (EMBL) in Heidelberg under the supervision of Prof. Dr Ulrich Scheer (Department of Cell and Developmental Biology/Zoology I, Bayerische Julius-Maximilians-Universität Würzburg). This work was completed between September 1999 and February 2003 and was supported by an EMBL predoctoral fellowship. The thesis is organized as a paper dissertation ("kumulative Dissertation"). The following publications are presented in the thesis: 1. Herold, A., Suyama, M., Rodrigues, J. P., Braun, I.C., Kutay, U., Carmo-Fonseca, M., Bork, P., and Izaurralde, E. (2000) TAP (NXF1) belongs to a multigene family of putative RNA export factors with a conserved modular architecture. Mol Cell Biol 20, 8996-9008. 2. Jun, L., Frints, S., Duhamel, H., Herold, A., Abad-Rodrigues, J., Dotti, C., Izaurralde, E., Marynen, P., Froyen, G. (2001) NXF5, a novel member of the nuclear RNA export factor family, is lost in a male patient with a syndromic form of mental retardation. Curr Biol 11, 1381-1391. 3. Herold, A., Klymenko, T., and Izaurralde, E. (2001) NXF1/p15 heterodimers are essential for mRNA nuclear export in Drosophila. RNA 7, 1768-1780. 4. Herold, A., Teixeira L., and Izaurralde, E. (2003) Genome-wide analysis of mRNA nuclear export pathways in Drosophila. Submitted. 5. Braun, I.C., Herold, A., Rode, M., Conti, E., and Izaurralde, E. (2001) Overexpression of TAP/p15 heterodimers bypasses nuclear retention and stimulates nuclear mRNA export. J Biol Chem 276, 20536-20543. 6. Braun, I. C., Herold, A., Rode, M., and Izaurralde, E. (2002) Nuclear export of mRNA by TAP/NXF1 requires two nucleoporin binding sites but not p15. Mol Cell Biol 22, 5405-5418. 7. Lange, B.M.H., Rebollo, E., Herold, A., and Gonzalez, C. (2002) Cdc37 is essential for chromosome segregation and cytokinesis in higher eukaryotes. EMBO J 21, 5364- 5374.
Page 1: The role of human and Drosophila NX
Page 5 and 6: Table of Contents Table of Contents
Page 7 and 8: Summary Summary 1 A distinguishing
Page 9 and 10: Summary 3 Crm1 resulted in decrease
Page 11 and 12: Zusammenfassung 5 NXF1 durch RNAi v
Page 13 and 14: 1 Introduction 1.1 Nucleocytoplasmi
Page 15 and 16: 1.1.4 The importin ββ-like family
Page 17 and 18: 1.2 The nuclear export of RNAs Intr
Page 19 and 20: Introduction 13 with the export of
Page 21 and 22: Introduction 15 What are the critic
Page 23 and 24: Introduction 17 mRNA export are ind
Page 25 and 26: Introduction 19 The NPC-binding dom
Page 27 and 28: Introduction 21 Association of the
Page 29 and 30: Introduction 23 could trigger ATP-d
Page 31 and 32: Introduction 25 Sub2p and Yra1p and
Page 33 and 34: Introduction 27 In S. cerevisiae, s
Page 35 and 36: Introduction 29 export block of bul
Page 37 and 38: Introduction 31 efficiently blocks
Page 39 and 40: 2 Results/Publications Results/Publ
Page 41 and 42: Results/Publications 35 shown to in
Page 43 and 44: VOL. 20, 2000 NXF MULTIGENE FAMILY
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VOL. 20, 2000 NXF MULTIGENE FAMILY
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Results/Publications 49 2.1.2 Paper
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Research Paper 1381 NXF5, a novel m
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Research Paper Loss of the NXF5 gen
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Figure 4 Research Paper Loss of the
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Results/Publications 63 with the nu
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RNA (2001), 7:1768-1780+ Cambridge
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1770 A. Herold et al. FIGURE 1. Com
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1772 A. Herold et al. FIGURE 3. Dep
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1774 A. Herold et al. FIGURE 5. Dep
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1776 A. Herold et al. FIGURE 7. hsp
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1778 A. Herold et al. 2001)+ Simila
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1780 A. Herold et al. Black BE, Hol
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Results/Publications 79 mRNAs had a
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Herold et al. Results/Publications
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Herold et al. (Supplemental Materia
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Herold et al. (Supplemental Materia
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A 10000 reference 1000 100 10 10000
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A 10 1 -10 3.07 (11) 2.37 4.74 (20)
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A B Northern blot dsRNA sd06908: cl
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GFP day4 NXF1 day2 NXF1 day4 p15 da
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Supplemental Table I. mRNAs not aff
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GH06306 1.86 1.49 2.60 1.65 2.95 2.
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Supplemental Table III: mRNAs that
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Supplemental Table IV: mRNAs that a
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2.3 Functional analysis of TAP/NXF1
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THE JOURNAL OF BIOLOGICAL CHEMISTRY
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20538 FIG. 1. Domain organization o
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20540 FIG. 4. TAP stimulates export
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20542 CRM1-mediated export of U snR
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Results/Publications 127 2.3.2 Pape
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MOLECULAR AND CELLULAR BIOLOGY, Aug
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VOL. 22, 2002 p15-INDEPENDENT NUCLE
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Results/Publications 143 2.4 Role o
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The EMBO Journal Vol. 21 No. 20 pp.
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B.M.H.Lange et al. somes at metapha
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B.M.H.Lange et al. Fig. 5. Aurora B
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B.M.H.Lange et al. Fig. 6. Aurora B
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B.M.H.Lange et al. released along t
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B.M.H.Lange et al. protein kinase i
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Discussion 157 strain, already poin
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Discussion 159 by a (second) UBA-li
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Discussion 161 gradual process requ
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Discussion 163 Although there is no
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Discussion 165 identify mRNAs which
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Human NXFs Discussion 167 While the
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Discussion 169 Therefore, DmNXF1 sh
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References References 171 Aitchison
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References 173 Gadal, O., Strauss,
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References 175 Katahira, J., Strass
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References 177 Murphy, R., Watkins,
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References 179 Strasser, K., Masuda
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Abbreviations Abbreviations 181 ARE
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Curriculum vitae Personal Details N
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Erklärung Hiermit erkläre ich ehr
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