Gonzalez-Rico, Susana; (1997) The role of RNA-binding proteins in the synthesis of ribosomal RNA in Mycobacterium tuberculosis. A study of the interactions of ribosomal protein S10 and NusB with the leader region of the single rrn operon. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

In spite of significant advances in treatment, tuberculosis remains the largest cause of death due to a single pathogen in the world. To understand the physiology of M.tuberculosis, the bacillus that causes the disease, is one of the biggest challenges of modern microbiology. M.tuberculosis, like other pathogenic mycobacteria, is characterized by its slow growth rate, and it is thought that slow growth is an important characteristic of the pathogenicity of these organisms. Since there is a strong correlation between the growth rate and ribosome synthesis, ribosomal RNA and ribosomal protein production are expected to be strongly regulated in these bacteria. In E. coli the synthesis of rRNA is believed to be the rate limiting step in ribosome synthesis. Several mechanisms have been found to regulate the transcription of rrn operons in these bacteria. For example, interaction of protein factors, specifically ribosomal protein S10 and NusB, with signals present in the leader region of the operon (boxA) has been shown to be necessary for efficient end-to-end transcription of the operon (antitermination). In order to further our understanding of the mechanisms used by pathogenic, slow-growing mycobacteria to regulate the synthesis of ribosomes, we have investigated the binding of mycobacterial homologues of ribosomal protein S10 and NusB to RNA molecules carrying a highly conserved sequence (including a boxA signal) of the leader region of the M.tuberculosis rrn operon. Mycobacterial homologues of ribosomal protein S10 and NusB have been identified, cloned, sequenced, expressed and purified. In order to study their interaction with the leader region of the rrn operon, RNA molecules carrying different sequences present in the leader region of the M.tuberculosis rrn operon were synthesized by in vitro transcription. The interaction between ribosomal protein S10, NusB and boxA RNA was studied by different techniques. Our results show that the binding of NusB to RNA containing the boxA sequence is enhanced by ribosomal protein S10. However, this phenomenon is largely non-specific for RNA molecules carrying the putative boxA element.

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