Unterschiedliche Protein- und RNA-Interaktionen von Roquin bedingen alternative Mechanismen posttranskriptioneller Genregulation

• Antragsteller: Professor Dr. Vigo Heissmeyer; Professor Dr. Dierk Niessing
• Fachliche Zuordnung: Allgemeine Genetik und funktionelle Genomforschung ; Biochemie ; Strukturbiologie ; Zellbiologie
• Förderung: Förderung von 2016 bis 2023
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 313381103

Zusammenfassung der Projektergebnisse

Our joint project demonstrated that mRNA regulation in T cells is orchestrated by the combined binding of defined combinations of RBPs. Beyond establishing it as a role model for the core topic of this SPP, i.e. the combinatorial code of RNAs, it may serve as an example for the potential to translate basic research into applied studies with therapeutic potential.

Projektbezogene Publikationen (Auswahl)

• Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation. Nature Structural & Molecular Biology, 21(8), 671-678.
  Schlundt, Andreas; Heinz, Gitta A; Janowski, Robert; Geerlof, Arie; Stehle, Ralf; Heissmeyer, Vigo; Niessing, Dierk & Sattler, Michael
  
• RNA recognition by Roquin in posttranscriptional gene regulation. WIREs RNA, 7(4), 455-469.
  Schlundt, Andreas; Niessing, Dierk; Heissmeyer, Vigo & Sattler, Michael
  
• Roquin recognizes a non-canonical hexaloop structure in the 3′-UTR of Ox40. Nature Communications, 7(1).
  Janowski, Robert; Heinz, Gitta A.; Schlundt, Andreas; Wommelsdorf, Nina; Brenner, Sven; Gruber, Andreas R.; Blank, Michael; Buch, Thorsten; Buhmann, Raymund; Zavolan, Mihaela; Niessing, Dierk; Heissmeyer, Vigo & Sattler, Michael
  
• Roquin Suppresses the PI3K-mTOR Signaling Pathway to Inhibit T Helper Cell Differentiation and Conversion of Treg to Tfr Cells. Immunity, 47(6), 1067-1082.e12.
  Essig, Katharina; Hu, Desheng; Guimaraes, Joao C.; Alterauge, Dominik; Edelmann, Stephanie; Raj, Timsse; Kranich, Jan; Behrens, Gesine; Heiseke, Alexander; Floess, Stefan; Klein, Juliane; Maiser, Andreas; Marschall, Susan; Hrabĕ de Angelis, Martin; Leonhardt, Heinrich; Calkhoven, Cornelis F.; Noessner, Elfriede; Brocker, Thomas; Huehn, Jochen; ... & Heissmeyer, Vigo
  
• Binding of NUFIP2 to Roquin promotes recognition and regulation of ICOS mRNA. Nature Communications, 9(1).
  Rehage, Nina; Davydova, Elena; Conrad, Christine; Behrens, Gesine; Maiser, Andreas; Stehklein, Jenny E.; Brenner, Sven; Klein, Juliane; Jeridi, Aicha; Hoffmann, Anne; Lee, Eunhae; Dianzani, Umberto; Willemsen, Rob; Feederle, Regina; Reiche, Kristin; Hackermüller, Jörg; Leonhardt, Heinrich; Sharma, Sonia; Niessing, Dierk & Heissmeyer, Vigo
  
• Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation. Nature Communications, 9(1).
  Essig, Katharina; Kronbeck, Nina; Guimaraes, Joao C.; Lohs, Claudia; Schlundt, Andreas; Hoffmann, Anne; Behrens, Gesine; Brenner, Sven; Kowalska, Joanna; Lopez-Rodriguez, Cristina; Jemielity, Jacek; Holtmann, Helmut; Reiche, Kristin; Hackermüller, Jörg; Sattler, Michael; Zavolan, Mihaela & Heissmeyer, Vigo
  
• Combinatorial recognition of clustered RNA elements by the multidomain RNA-binding protein IMP3. Nature Communications, 10(1).
  Schneider, Tim; Hung, Lee-Hsueh; Aziz, Masood; Wilmen, Anna; Thaum, Stephanie; Wagner, Jacqueline; Janowski, Robert; Müller, Simon; Schreiner, Silke; Friedhoff, Peter; Hüttelmaier, Stefan; Niessing, Dierk; Sattler, Michael; Schlundt, Andreas & Bindereif, Albrecht
  
• Immune homeostasis and regulation of the interferon pathway require myeloid-derived Regnase-3. Journal of Experimental Medicine, 216(7), 1700-1723.
  von Gamm, Matthias; Schaub, Annalisa; Jones, Alisha N.; Wolf, Christine; Behrens, Gesine; Lichti, Johannes; Essig, Katharina; Macht, Anna; Pircher, Joachim; Ehrlich, Andreas; Davari, Kathrin; Chauhan, Dhruv; Busch, Benjamin; Wurst, Wolfgang; Feederle, Regina; Feuchtinger, Annette; Tschöp, Matthias H.; Friedel, Caroline C.; Hauck, Stefanie M.; ... & Glasmacher, Elke
  
• Staufen2-mediated RNA recognition and localization requires combinatorial action of multiple domains. Nature Communications, 10(1).
  Heber, Simone; Gáspár, Imre; Tants, Jan-Niklas; Günther, Johannes; Moya, Sandra M. Fernandez; Janowski, Robert; Ephrussi, Anne; Sattler, Michael & Niessing, Dierk
  
• Validation strategies for antibodies targeting modified ribonucleotides. RNA, 26(10), 1489-1506.
  Weichmann, Franziska; Hett, Robert; Schepers, Aloys; Ito-Kureha, Taku; Flatley, Andrew; Slama, Kaouthar; Hastert, Florian D.; Angstman, Nicholas B.; Cardoso, M. Cristina; König, Julian; Hüttelmaier, Stefan; Dieterich, Christoph; Canzar, Stefan; Helm, Mark; Heissmeyer, Vigo; Feederle, Regina & Meister, Gunter
  
• Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation. Nature Communications, 12(1).
  Hoefig, Kai P.; Reim, Alexander; Gallus, Christian; Wong, Elaine H.; Behrens, Gesine; Conrad, Christine; Xu, Meng; Kifinger, Lisa; Ito-Kureha, Taku; Defourny, Kyra A. Y.; Geerlof, Arie; Mautner, Josef; Hauck, Stefanie M.; Baumjohann, Dirk; Feederle, Regina; Mann, Matthias; Wierer, Michael; Glasmacher, Elke & Heissmeyer, Vigo
  
• Disrupting Roquin-1 interaction with Regnase-1 induces autoimmunity and enhances antitumor responses. Nature Immunology, 22(12), 1563-1576.
  Behrens, Gesine; Edelmann, Stephanie L.; Raj, Timsse; Kronbeck, Nina; Monecke, Thomas; Davydova, Elena; Wong, Elaine H.; Kifinger, Lisa; Giesert, Florian; Kirmaier, Martin E.; Hohn, Christine; de Jonge, Laura S.; Pisfil, Mariano Gonzalez; Fu, Mingui; Theurich, Sebastian; Feske, Stefan; Kawakami, Naoto; Wurst, Wolfgang; Niessing, Dierk & Heissmeyer, Vigo
  
• Cooperation of RNA-Binding Proteins – a Focus on Roquin Function in T Cells. Frontiers in Immunology, 13(c(2022, 2, 18)).
  Behrens, Gesine & Heissmeyer, Vigo
  
• The function of Wtap in N6-adenosine methylation of mRNAs controls T cell receptor signaling and survival of T cells. Nature Immunology, 23(8), 1208-1221.
  Ito-Kureha, Taku; Leoni, Cristina; Borland, Kayla; Cantini, Giulia; Bataclan, Marian; Metzger, Rebecca N.; Ammann, Gregor; Krug, Anne B.; Marsico, Annalisa; Kaiser, Stefanie; Canzar, Stefan; Feske, Stefan; Monticelli, Silvia; König, Julian & Heissmeyer, Vigo
  
• Depletion of the RNA-binding protein PURA triggers changes in posttranscriptional gene regulation and loss of P-bodies. Nucleic Acids Research, 51(3), 1297-1316.
  Molitor, Lena; Klostermann, Melina; Bacher, Sabrina; Merl-Pham, Juliane; Spranger, Nadine; Burczyk, Sandra; Ketteler, Carolin; Rusha, Ejona; Tews, Daniel; Pertek, Anna; Proske, Marcel; Busch, Anke; Reschke, Sarah; Feederle, Regina; Hauck, Stefanie M; Blum, Helmut; Drukker, Micha; Fischer-Posovszky, Pamela; König, Julian; ... & Niessing, Dierk
  
• The thymocyte-specific RNA-binding protein Arpp21 provides TCR repertoire diversity by binding to the 3’-UTR and promoting Rag1 mRNA expression. Nature Communications, 15(1).
  Xu, Meng; Ito-Kureha, Taku; Kang, Hyun-Seo; Chernev, Aleksandar; Raj, Timsse; Hoefig, Kai P.; Hohn, Christine; Giesert, Florian; Wang, Yinhu; Pan, Wenliang; Ziętara, Natalia; Straub, Tobias; Feederle, Regina; Daniel, Carolin; Adler, Barbara; König, Julian; Feske, Stefan; Tsokos, George C.; Wurst, Wolfgang; ... & Heissmeyer, Vigo