Many reports point to the existence of two functionally distinct genome compartments in the mammalian nucleus: Biologically active and transcribed chromatin versus inactive heterochromatin. Notably, the structural segregation of these two compartments is not simply the consequence of the gene expression state of a given locus. Rather, the nuclear architecture actively participates in the dynamic regulation of activity and determines specific gene-expression programs and thereby shapes cellular functions. Interestingly, many aspects of the underlying dynamic nuclear architecture involve RNA as an effector molecule with structural functionality. Recent work from our laboratory has demonstrated that a specific fraction of nuclear-retained RNAs termed chromatin interacting RNAs (ciRNAs) is an essential structural component of active transcription compartments in the mammalian cell nucleus (Caudron-Herger et al., 2011; Caudron-Herger & Rippe, 2012). According to the current working model, a network is formed between RNAP II, perichromatin fibrils, nascent RNA transcripts, ciRNAs and chromatin binding proteins that interact with each other to decondense chromatin on the µm length scale so that it can be transcribed. The focus of my project is to elucidate how RNA contributes to maintaining this open chromatin structure. We have identified a number of candidate ciRNAs and will use a combination of experimental and bioinformatic approaches to further characterized these candidates. Elucidating on the mechanism by which RNA organizes active transcription compartments will have far reaching implications for both the fields of nuclear structure and RNA biology in as much as they reveal a previously unknown structural function of RNA as a genome organizer. It is anticipated that this work will significantly increase our understanding of the structure-function relation between nuclear architecture and gene expression.
- since 02/2016: PostDoc in the laboratory of PD R. Karsten Rippe, Research Group Genome Function and Organization, BioQuant, German Cancer Research Center (DKFZ), Heidelberg
- 01/2012 – 02/2016: PhD student in the laboratory of PD R. Karsten Rippe, Research Group Genome Function and Organization, BioQuant, German Cancer Research Center (DKFZ), Heidelberg
Title: "A 3'-UTR sequence element modifies chromatin and regulates alternative splicing"
- 10/2009 – 10/2011: Master of Molecular Biosciences, Major Cancer Biology at the University of Heidelberg and at the German Cancer Research Center (DKFZ)
Master Thesis in the group of Prof. Dr. Peter Lichter, Department of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg
Title: "Impact of Phosphatase Silencing on Chemo- and Radioresistance in Glioblastoma Stem-Like Cells"
- 09/2006 – 07/2009: Bachelor of Science, Molecular Life Sciences, Maastricht University, The Netherlands
Caudron-Herger M, Pankert T, Seiler J, Nemeth A, Voit R, Grummt I, Rippe K (2015) Alu element-containing RNAs maintain nucleolar structure and function. EMBO J 34: 2758-2774
Bageritz J, Puccio L, Piro RM, Hovestadt V, Phillips E, Pankert T, Lohr J, Herold-Mende C, Lichter P, Goidts V (2014) Stem cell characteristics in glioblastoma are maintained by the ecto-nucleotidase E-NPP1. Cell Death Differ 21: 929-940
Borner K, Niopek D, Cotugno G, Kaldenbach M, Pankert T, Willemsen J, Zhang X, Schurmann N, Mockenhaupt S, Serva A, Hiet MS, Wiedtke E, Castoldi M, Starkuviene V, Erfle H, Gilbert DF, Bartenschlager R, Boutros M, Binder M, Streetz K, Krausslich HG, Grimm D (2013) Robust RNAi enhancement via human Argonaute-2 overexpression from plasmids, viral vectors and cell lines. Nucleic Acids Res 41: e199