Regulation of Coding and Non-coding Genes: New insights obtained through analysis of high-throughput sequencing data

The genetic code of a cell is kept in its DNA. However, a vast number of functions of a cell are carried out by proteins. Through gene expression the genetic code can be expressed and give rise to proteins. The expression of genes into proteins follows two steps: transcription of DNA into RNA and translation of (messenger-)RNA into proteins. This thesis concerns these two steps in gene expression, which are very different from a molecular point-ofview

TGFβ1-induced leucine limitation uncovered by differential ribosome codon reading

Cancer cells modulate their metabolic networks to support cell proliferation and a higher demand of building blocks. These changes may restrict the availability of certain amino acids for protein synthesis, which can be utilized for cancer therapy. However, little is known about the amino acid demand changes occurring during aggressive and invasive stages of cancer. Recently, we developed diricore, an approach based on ribosome profiling that can uncover amino acid limitations. Here, we applied diricore to a cellular model in which epithelial breast cells respond rapidly to TGFβ1, a cytokine essential for cancer progression and metastasis, and uncovered shortage of leucine. Further analyses indicated that TGFβ1 treatment of human breast epithelial cells reduces the expression of SLC3A2, a subunit of the leucine transporter, which diminishes leucine uptake and inhibits cell proliferation. Thus, we identified a specific amino acid limitation associated with the TGFβ1 response, a vulnerability that might be associated with aggressiveness in cancer