Group Neus Visa

The individual steps of gene expression in a eukaryotic cell are relatively well characterized at the biochemical level, and the enzymes and molecular complexes involved in each step of the process have been identified. However, much remains to be understood about how these individual reactions are coordinated and regulated in the living cell. Our research is focused on the following specific questions.

Mechanisms of quality control (QC) of mRNA biogenesis

Eukaryotes have developed QC mechanisms to eliminate defective RNAs. We have shown that specific mRNA-binding proteins recruit QC factors to the pre-mRNA during transcription. We intend to continue these studies to understand how the QC machinery interacts with the (pre-)mRNA at different stages of gene expression, and how the mRNA-binding proteins contribute to specify the quality of the transcripts.

Crosstalk between transcription, chromatin structure and pre-mRNA processing

We have shown that mRNA-binding proteins participate in the recruitment of chromatin factors that regulate transcription. We have also shown that the SWI/SNF chromatin remodeling factor binds to the nascent pre-mRNA and affects alternative splicing. We intend to study the molecular mechanisms by which chromatin factors regulate pre-mRNA processing.

We use two insect model systems that offer complementary possibilities. One of them is the midge Chironomus tentans, which is a useful organism for in situ studies using immunofluorescence and immuno-electron microscopy. In collaboration with Lars Wieslander and with scientists at the SciLifeLab, we are working on the genome and transcriptome sequences of C. tentans, which will expand the experimental possibilities for work with this model organism. We also use the S2 cells of the fruitfly Drosophila melanogaster for functional and genome-wide studies including RNAi, proteomics and transcriptomics.

Mechanisms of action of 5-fluorouracil (5FU)

We are also working on a project aimed at characterizing the mechanisms of action of 5FU, a drug commonly used for the treatment of solid tumors. We use human cell lines and we apply high-throughput mass-spectrometry methods. It is well established that multiple mechanisms contribute to the cytotoxicity of 5FU, and recent studies indicate that RNA-mediated responses contribute significantly to the therapeutic properties of this drug. We are trying to pinpoint these mechanisms in order to better understand the cytotoxicity of 5FU. Our studies should also help to better understand the cellular mechanisms of stress response at the RNA level.

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