Endoribonucleases
Ribonucleases (RNases) are enzymes involved in the processing and degradation of RNA molecules, allowing the recycling of ribonucleotides in the cell [1-3]. In recent years, RNases have been shown as powerful tools to study protein structure, folding and stability, and enzyme catalysis, being also relevant from a medical point of view. Studies involving these enzymes have already rendered two Nobel prizes.
Pathogenic bacteria are responsible for severe forms of disease worldwide. In order to invade and establish inside the host cells, they need to readily adapt to environmental challenges. This adaptation requires rapid adjustments in RNA levels. RNA availability and stability has long been emerged as a major player controlling the expression of virulence factors that allow pathogenic bacteria to infect their hosts [4]. Hence, RNases, by controlling RNA levels in the cell, play a crucial role in pathogenesis.
Mycobacterium tuberculosis remains the leading cause of mortality from a single infectious organism. The increasing prevalence of drug-resistant bacteria represents a serious health problem nowadays. The development of new antimicrobials is a major strategy towards overcoming the problems with drug resistance, as new compounds can offer novel modes of action to which target pathogens are initially susceptible.
Work done in our Team have identified two putative members of the RNB-family of enzymes in M. tuberculosis which were subject of a thorough biochemical and biophysical characterization. Our ultimate goal is the three-dimensional structure determination of the RNase enzymes from M. tuberculosis, either by X-ray crystallography or cryo-electron microscopy. The obtained results will lead to the unraveling of the mechanism of action of these enzymes and climactically to the development of new antimicrobials to fight Mycobacterium infection.
This project is in Collaboration with Doctor Rute G. Matos from the Laboratory of Control of Gene Expression headed by Prof. Doctor Cecília M. Arraiano.
[1] Nicholson, A.W. Function, mechanism and regulation of bacterial ribonucleases. FEMS Microbiol Rev 23, 371-90 (1999).
[2] Régnier, P. & Arraiano, C.M. Degradation of mRNA in bacteria: emergence of ubiquitous features. Bioessays 22, 235-44 (2000).
[3] Deutscher, M.P. Promiscuous exoribonucleases of Escherichia coli. J Bacteriol 175, 4577-83 (1993).
[4] Eidem, T.M., Roux, C.M. & Dunman, P.M. RNA decay: a novel therapeutic target in bacteria. Wiley Interdiscip Rev RNA 3, 443-54 (2012).
