Entschlüsselung des menschlichen nonsense-vermittelten mRNA-Abbaus (NMD)

• Antragsteller: Professor Dr. Christoph Dieterich; Professor Dr. Niels H. Gehring
• Fachliche Zuordnung: Allgemeine Genetik und funktionelle Genomforschung ; Zellbiologie
• Förderung: Förderung von 2016 bis 2024
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 313641849

Zusammenfassung der Projektergebnisse

Altogether, our studies demonstrated that different mRNP components play crucial roles in determining mRNA stability and splicing fidelity, thereby influencing gene expression. This supports our initial idea of the mRNP code, postulating that various RNA-bound determinants, including sequence elements, RNA modifications, and RNA-binding proteins, impact posttranscriptional gene regulation. Several publications are still pending i.e. under review or in preparation.

Projektbezogene Publikationen (Auswahl)

• Deciphering the mRNP Code: RNA-Bound Determinants of Post-Transcriptional Gene Regulation. Trends in Biochemical Sciences, 42(5), 369-382.
  Gehring, Niels H.; Wahle, Elmar & Fischer, Utz
  
• Exon Junction Complexes Suppress Spurious Splice Sites to Safeguard Transcriptome Integrity. Molecular Cell, 72(3), 482-495.e7.
  Boehm, Volker; Britto-Borges, Thiago; Steckelberg, Anna-Lena; Singh, Kusum K.; Gerbracht, Jennifer V.; Gueney, Elif; Blazquez, Lorea; Altmüller, Janine; Dieterich, Christoph & Gehring, Niels H.
  
• CASC3 promotes transcriptome-wide activation of nonsense-mediated decay by the exon junction complex. Nucleic Acids Research, 48(15), 8626-8644.
  Gerbracht, Jennifer V; Boehm, Volker; Britto-Borges, Thiago; Kallabis, Sebastian; Wiederstein, Janica L; Ciriello, Simona; Aschemeier, Dominik U; Krüger, Marcus; Frese, Christian K; Altmüller, Janine; Dieterich, Christoph & Gehring, Niels H
  
• SMG5-SMG7 authorize nonsense-mediated mRNA decay by enabling SMG6 endonucleolytic activity. Nature Communications, 12(1).
  Boehm, Volker; Kueckelmann, Sabrina; Gerbracht, Jennifer V.; Kallabis, Sebastian; Britto-Borges, Thiago; Altmüller, Janine; Krüger, Marcus; Dieterich, Christoph & Gehring, Niels H.
  
• Exon junction complex-associated multi-adapter RNPS1 nucleates splicing regulatory complexes to maintain transcriptome surveillance. Nucleic Acids Research, 50(10), 5899-5918.
  Schlautmann, Lena P; Lackmann, Jan-Wilm; Altmüller, Janine; Dieterich, Christoph; Boehm, Volker & Gehring, Niels H
  
• Human UPF3A and UPF3B enable fault‐tolerant activation of nonsense‐mediated mRNA decay. The EMBO Journal, 41(10).
  Wallmeroth, Damaris; Lackmann, Jan‐Wilm; Kueckelmann, Sabrina; Altmüller, Janine; Dieterich, Christoph; Boehm, Volker & Gehring, Niels H.