Projects Offered

1 PhD project offered in the IPP winter call Molecular Mechanisms in Genome Stability & Gene Regulation

Scientific Background

Nuclear mRNA export is an essential step in eukaryotic gene expression, ensuring that mature transcripts are delivered from the nucleus to the cytoplasm for translation. Multiple challenges are faced in this process: How are mRNAs discriminated against all other nuclear RNAs? How does the cell ensure that only fully matured mRNAs are exported? How are faulty mRNAs and transcription byproducts targeted for degradation? At the core of mRNA nuclear export works an evolutionary conserved machinery centered on a large protein complex: TREX. While we recently uncovered a mechanistic framework of the core of this pathway, the regulatory layers, connections to diverse cellular processes and repurposing for the export of non-canonical mRNAs remains cryptic. 

PhD Project: “Mechanistic insights into novel mRNA export complexes”

During my postdoc I discovered that the TREX-complex member and RNA clampase UAP56 functions at the heart of nuclear mRNA export and orchestrates nuclear remodeling steps through its ATP-dependent RNA binding cycle. Intriguingly, I identified multiple novel direct interactors of UAP56, which appear to either stall or shortcut mRNA export. 

Using a combination of biochemical reconstitution, genetic approaches in the powerful model systems zebrafish and fruit fly, and structural biology (including AlphaFold predictions and cryo-EM), we will dissect the roles of these novel mRNA export regulators and define how they interface with other nuclear RNA processes. In addition, we will apply cellular assays (export reporters, RNA-FISH), proteomics, transcriptomics and high-resolution microscopy to corroborate our findings. By integrating molecular biology, genetics, and biophysical approaches, we aim to obtain new mechanistic insights into the regulation of mRNA export, one of the central pathways of gene expression.

If you are interested in this project, please select Hohmann as your group preference in the IPP application platform.

Publications relevant to this project 

Hohmann U, Graf M, Schellhaas U, Pacheco-Fiallos B, Fin L, Riabov-Bassat D, Pühringer T, Szalay MF, Tirian L, Handler D, Brennecke J, Plaschka C, A molecular switch orchestrates the export of human messenger RNA. BioRxiv (2024). Link (under revision in Nature)

Pühringer T*, Hohmann U*, Fin L, Pacheco-Fiallos B, Schellhaas U, Brennecke J, Plaschka C, Structure of the human core transcription-export complex reveals a hub for multivalent interactions. eLife. 9, e61503 (2020) Link * indicates equal contribution

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