Regulation of antibiotic production by ncRNA and signaling molecules in Streptomyces coelicolor

PhD ceremony: Mr. D. D'Alia, 14.45 uur, Academiegebouw, Broerstraat 5, Groningen

Title: Regulation of antibiotic production by ncRNA and signaling molecules in Streptomyces coelicolor

Promotor(s): prof. L. Dijkhuizen, prof. E. Takano

Faculty: Mathematics and Natural Sciences

Regulatory non-coding RNAs (ncRNAs) are a recently discovered class of DNA transcripts that lack any protein-coding potential and regulate protein translation by annealing to their target messenger RNA (mRNA) molecule. They are considered as key regulators of many cell processes such as virulence, cell communication and secondary metabolite production. Davide d’Alia has predicted, by computational analysis, a large number of ncRNAs especially overlapping with protein-coding genes, which are not commonly found in bacteria, in the antibiotic-producing soil bacterium Streptomyces coelicolor. The presence of some of them was confirmed by him experimentally. One of these ncRNAs, which regulates the mRNA encoding the enzyme glutamine synthetase I (GSI) was analysed in more detail. Additional copies of the GSI ncRNA led to a decrease in the amount of GSI protein and caused a drastic decrease in growth and antibiotic production. This is the first report of a functional ncRNA in Streptomyces and also prompts a functional role for the non-coding transcripts in bacterial cells.

To show that also artificial ncRNAs can be used as a tool to decrease protein synthesis, in a fashion similar to the eukaryotic RNA interference, several ncRNAs for the mRNA encoding the regulator ScbR were constructed by d’Alia. Additional copies of these ncRNAs caused a strong decrease in the amount of ScbR protein synthesized in the cell. His work shows that the ncRNA method can be used as a new technique in bacterial cells to control protein expression.