Mechanisms of human mRNA packaging and export

The export of mRNA from the nucleus to the cytoplasm is an essential step in eukaryotic gene expression. This process requires that only fully processed mRNAs are exported, while undesirable RNAs are degraded in the nucleus.

This selectivity is proposed to be mediated by the packaging of mature mRNA by export factors, protecting mRNA from nuclear degradation and licensing it for export to the cytoplasm. However, this model has not been directly and thoroughly tested.

Furthermore, the full range of factors that promote the selective packaging and export of mRNA is not yet known.In this proposal, I propose an interdisciplinary and collaborative project that addresses these two major outstanding topics in gene expression.

To address the role of mRNA packaging as a key driver of nuclear export versus degradation, I propose to employ a time-resolved transcriptomics and modeling approach to simultaneously measure nuclear mRNA export and degradation rates, modulating mRNA compaction state with rapid protein degradation.

Next, I will employ ORF-tag, a novel genome-wide gain-of-function screening method that will determine the full list of proteins sufficient to drive nuclear mRNA export.

I will then characterize promising novel export factors using transcriptomic and biochemical approaches to integrate these proteins into our structural understanding of nuclear mRNA packaging.

The diverse methodology of this project, the technical support both within the host labs and the facilities on campus, and the high quality of training resources and supervision available will facilitate my own development as a scientist and prepare me perfectly to establish my own independent research group.

Through my relocation from the UK to Austria, I will expand the European RNA biology network, forging future international collaborations.

My background in molecular and computational biology will allow me to execute this impactful project and answer fundamental questions in gene expression.