From the moment when a mRNA is first transcribed by the RNA polymerase, RNA-binding proteins associate with this transcript and influence its fate.
One protein complex in particular, called the exon junction complex (EJC), is deposited on the mRNA during splicing.
The EJC remains bound on the mRNA until it is displaced in the cytoplasm by ribosomes.
Until then, the EJC regulates alternative splicing, enhances nuclear mRNA export, stimulates translation and ultimately, is involved in quality control (see nonsense-mediated mRNA decay).
We currently investiage how the EJC is assembled in the first place, which factors are required for this, and how the EJC exerts its many functions on gene expression.
Key publications:Gehring NH, Wahle E, Fischer U.
To maintain the correct translation of proteins in the cell, quality control mechanisms constantly monitor each step of gene expression.
One of these mechanisms is the nonsense-mediated mRNA decay pathway, or short NMD.
If due to mutations or other reasons, such as mistakes during pre-mRNA processing, a transcript contains a premature translation termination codon (PTC),
this mRNA is detected by NMD and consequently degraded. Thereby, NMD generally protects the cell by preventing the translation of truncated proteins.
Nevertheless, if the PTC-containing mRNAs in principle encode for partially functional proteins, as it is the case in certain diseases, the clinical phenotype could be alleviated by blocking NMD specifically. To better understand, how NMD is activated, how PTC-containing mRNAs are distinguished from normal ones, and how the transcripts are degraded in the end, we use molecular-biological and biochemical experimental approaches in cultured human cells.
Key publications:Ottens F, Boehm V, Sibley CR, Ule J, Gehring NH.
Before an mRNA is translated in the cytoplasm, it has to be processed in the nucleus and transported to the cytoplasm. The export of mature mRNAs is tightly linked to nuclear pre-mRNA processing to ensure that only correctly processed transcripts are translated. The recruitment of the general mRNA export receptor NXF1/NXT1 to spliced mRNA involves different adaptor proteins. Some of these adaptor proteins (e.g. ALYREF) interact with the exon junction complex, which therefore provides a link between pre-mRNA splicing and export.
Key publications:Gromadzka AM, Steckelberg AL, Singh KK, Hofmann K, Gehring NH.
Marie Charlotte Marx
Please send inquiries for Bachelor and Master theses or laboratory modules including a short CV to Niels Gehring.