Dokument: The mRNA stability Regulator Khd4 determines infectious hyphae development in Ustilago maydis
Titel: | The mRNA stability Regulator Khd4 determines infectious hyphae development in Ustilago maydis | |||||||
URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=64612 | |||||||
URN (NBN): | urn:nbn:de:hbz:061-20240122-085737-6 | |||||||
Kollektion: | Dissertationen | |||||||
Sprache: | Englisch | |||||||
Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
Medientyp: | Text | |||||||
Autor: | Sankaranarayanan, Srimeenakshi [Autor] | |||||||
Dateien: |
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Beitragende: | Prof. Dr. Feldbrügge, Michael [Gutachter] Prof. Dr. Schaal, Heiner [Gutachter] | |||||||
Stichwörter: | fungal pathogen/ ER/ membrane trafficking / mRNA stability / gene expression regulation/ hyperTRIBE/ hypha/ Khd4 / polar growth / plant pathogenicity | |||||||
Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
Beschreibung: | Fungal pathogens cause severe diseases, affecting public health, wildlife, and agriculture. A key for virulence in many fungal pathogens lies in their capacity for morphological plasticity, regulated through precise gene expression control. Understanding these infection strategies, particularly at the level of DNA and RNA, is vital to combat fungal diseases. However, our knowledge of the spatiotemporal regulation of gene expression at the RNA level in the fungal kingdom remains limited. In Ustilago maydis, the causative agent of corn smut, the morphological transition from yeast to hyphal growth is essential for infection. Previously, it was discovered that the multi-KH domain RNA-binding protein (RBP) Khd4 is important for morphogenesis and pathogenesis in U. maydis. Khd4 recognizes the AUACCC sequence via its KH domains 5 and 6. Failure to recognize the sequence by mutating these RNA-binding domains caused aberrant cell morphology, disturbed hyphae formation, and reduced virulence. However, the direct mRNA targets of Khd4 and its corresponding function remained unknown.
Presented in this thesis is the investigation into the regulatory role of Khd4 in determining infectious hyphae formation in U. maydis. To identify Khd4 mRNA targets, the RNAproximity labeling hyperTRIBE approach was employed, which involves fusing the RNA-editing ADAR enzyme to the RBP to mark the target mRNA. Validation using Rrm4, a well-studied RBP in U. maydis, demonstrated the effectiveness of hyperTRIBE in identifying known Rrm4-mRNA interactions. This in vivo approach revealed that Khd4 selectively binds mRNAs encoding regulatory proteins involved in membrane trafficking via the AUACCC motif. Khd4 degrades these mRNAs by specifically interacting with its AUACCC element in the 3ยด UTR. This precise mRNA decay process dictates the induction kinetics of these mRNAs, enabling faster attainment of new steadystate levels after transcriptional induction, and rapid clearance after transcriptional shutoff. Consequently, in the absence of Khd4, membrane trafficking is dysregulated, resulting in fragmented vacuoles, affecting polar growth. Hence, Khd4 unites target mRNAs encoding regulatory proteins into membrane trafficking mRNA regulon, orchestrating the dynamics of intracellular transport crucial for hyphal growth. Studying Khd4 localization revealed that the protein exhibits cortical localization under heat stress, reminiscing that of the endoplasmic reticulum. Given the central role of ER in membrane trafficking, it is conceivable that Khd4 might regulate a subset of its target mRNAs in the vicinity of ER. In essence, the RBP Khd4 regulates infectious hyphae development by determining the exact levels of regulatory proteins crucial for this process. | |||||||
Lizenz: | ![]() Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Biologie » Mikrobiologie | |||||||
Dokument erstellt am: | 22.01.2024 | |||||||
Dateien geändert am: | 22.01.2024 | |||||||
Promotionsantrag am: | 07.11.2023 | |||||||
Datum der Promotion: | 18.12.2023 |