Research Topics and Financial Support

RNA Cis-elements and Trans-acting factors

We study structure-function and regulation of selected RNA-binding proteins, endoribonucleases, exoribonucleases, miRNAs, components of the m6A methyltransferase complex as well as their cofactors and downstream effectors. We define the transcriptome-interacting proteome (RBPome) and ask which proteins are in close proximity in T cells and cooperate functionally to control specific mRNA targets. Ongoing work of our group describes m6A methylation of RNA as well as the interaction of RNA-binding proteins with the transcriptome at near-nucleotide resolution in T cells. These studies will provide a detailed understanding of the post-transcriptional drivers and their molecular interactions in T cells and enable future therapeutic modulation of T cell function in autoimmune or autoinflammatory diseases as well as anti-tumor responses.

These aspects of our work receive funding from the DFG (Projects 444891219, 432656284, 313381103).

Selected publications:

Hoefig, K.P., Reim, A., Gallus, C. et al. Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation. Nat Commun 12, 5208 (2021). https://doi.org/10.1038/s41467-021-25345-5

Essig, K. et al. Roquin targets mRNAs in a 3'-UTR-specific manner by different modes of regulation. Nat Commun 9, 3810, doi:10.1038/s41467-018-06184-3 (2018).

Rehage, N. et al. Binding of NUFIP2 to Roquin promotes recognition and regulation of ICOS mRNA. Nat Commun 9, 299, doi:10.1038/s41467-017-02582-1 (2018).

Janowski, R. et al. Roquin recognizes a non-canonical hexaloop structure in the 3'-UTR of Ox40. Nat Commun 7, 11032, doi:10.1038/ncomms11032 (2016).

Warth, S. C. et al. Induced miR-99a expression represses Mtor cooperatively with miR-150 to promote regulatory T-cell differentiation. EMBO J 34, 1195-1213, doi:10.15252/embj.201489589 (2015).

Schlundt, A. et al. Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation. Nat Struct Mol Biol 21, 671-678, doi:10.1038/nsmb.2855 (2014).

Jeltsch, K. M. et al. Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote T(H)17 differentiation. Nat Immunol 15, 1079-1089, doi:10.1038/ni.3008 (2014).

Hoefig, K. P. et al. Eri1 degrades the stem-loop of oligouridylated histone mRNAs to induce replication-dependent decay. Nat Struct Mol Biol 20, 73-81, doi:10.1038/nsmb.2450 (2013).

Glasmacher, E. et al. Roquin binds inducible costimulator mRNA and effectors of mRNA decay to induce microRNA-independent post-transcriptional repression. Nat Immunol 11, 725-733, doi:10.1038/ni.1902 (2010).

Ansel, K. M. et al. Mouse Eri1 interacts with the ribosome and catalyzes 5.8S rRNA processing. Nat Struct Mol Biol 15, 523-530, doi:10.1038/nsmb.1417 (2008).