Projektbeschreibung
Erforschung der Regulierung der Genexpression
Zellen regulieren die Genexpression in hohem Maße zeitlich und räumlich, um sicherzustellen, dass die richtigen Proteine zur richtigen Zeit und am richtigen Ort produziert werden. Die Regulierung der Genexpression ist ein komplexer Prozess, der ein vielschichtiges Zusammenspiel von Regulierungselementen wie Transkriptionsfaktoren, epigenetischen Veränderungen und nicht-kodierenden RNAs umfasst. Das Team des vom Europäischen Forschungsrat finanzierten Projekts moreRNA wird sich auf die Reifung von microRNAs und die Auswirkungen von Ereignissen der direkten RNA-Methylierung auf die Genexpression konzentrieren. Die Forschungsgruppe wird molekular- und zellbiologische Verfahren einsetzen, um die Rolle des Methylierungspfads bei der Regulierung kodierender und nicht-kodierender RNAs zu analysieren. Insgesamt werden mithilfe des Projekts bisher unbekannte Genexpressionsfaktoren und Regulierungspfade beleuchtet.
Ziel
Coding and non-coding RNAs are regulated at numerous levels. For example, microRNA (miRNA) expression can be influenced at various steps of biosynthesis. Furthermore, it has been reported that direct RNA methylation events can also affect gene expression in many different organisms and systems. The aim of this project is to identify and characterize factors that affect the maturation of miRNAs. We will employ biochemical pull down assays to isolate specific binding partners of different miRNA species. We will analyze the physiological role of these factors using molecular or cell biological approaches. Molecular details of pre-miRNA-protein interactions will be investigated by x-ray crystallography. In addition, we will decipher the role of the m6A methylation pathway on the regulation of coding and non-coding RNAs. Writers, readers and erasers of this modification have been identified. However, not much is known about the composition of specific protein complexes as well as the atomic structure of these factors. Thus, we will functionally and structurally characterize known and putative novel factors of the m6A methylation pathway in human cells. Furthermore, using our biochemical pull down approach employed for the identification of pre-miRNA processing factors, we will identify reader proteins of several types of RNA modification that have not been investigated so far. The proposed project will elucidate the regulation of gene expression by small RNAs or direct RNA methylation and will add so far unknown components to these important regulatory pathways.
Wissenschaftliches Gebiet
- natural sciencesearth and related environmental sciencesgeologymineralogycrystallography
- medical and health sciencesclinical medicineoncology
- natural sciencesbiological sciencesgeneticsRNA
- natural sciencesbiological sciencesgeneticsgenomes
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-COG - Consolidator GrantGastgebende Einrichtung
93053 Regensburg
Deutschland