"Modifier view of the bacterial ribosome" ("Bakteriaalne ribosoom modifitseeritud nukleosiidide vaatevinklist"
Thesis supervisor: TÜ MRI professor Jaanus Remme ja vanemteadur Aivar Liiv.
Opponent: Professor Roland K. Hartmann, Farmatseutilise Keemia Instituut, Philipps'i Ülikool Marburgis, Marburg, Saksamaa.
Ribosomes are tiny machines that make proteins using the information stored in genes. The structure and mechanism of ribosomes is similar in all cells, but bacterial and eukaryotic (including human) ribosomes differ in details, eukaryotic ones are bigger, for instance. Ribosomes have a complicated structure; they are made of a large subunit and a small subunit both of which are made of ribonucleic acids (rRNA) and proteins. rRNA gives most of the mass to the ribosomes. Since it is both technically and ethically easier to study bacteria, most of the information about the structure and mechanisms of ribosomes as well as making the ribosomes themselves comes from them. The rRNA molecules are long chains put together of ribonucleosides (adenosine, guanosine, cytidine, and uridine). However, during making of the ribosomes but after the rRNA chain is already put together, some of the nucleosides in the chain are altered by specific proteins called modification enzymes. The altered nucleosides are called modified nucleosides and they are present in important parts of all ribosomes. However, the role of the modified nucleosides is unknown for the most part. We found that that the bacterial (Escherichia coli) modification enzyme RlmH is special because it modifies pseudouridine, which already is a modified nucleoside and is located in a very important part of the large subunit. In addition, RlmH is special because it is the only modification enzyme that requires both subunits of the ribosome to modify rRNA. In fact, RlmH modifies an almost finished ribosome that is possibly already making proteins. We have studied the conditions that RlmH requires to modify the rRNA and the mechanism behind its uniqueness.