Role of translational fidelity in cellular physiology of oral streptococci

Ribosomes are complex ribonucleoproteins essential for protein synthesis in the cell. In prokaryotes, mature ribosomes contain proteins (r-proteins) and RNA (rRNA) that are assembled into the mature 70S ribosome. The 70S ribosomes are made by two subunits, designated as the 30S (small) and the 50S ribosome (large) subunits. The small subunit is composed of the 16S ribosomal RNA (rRNA) and over 20 core r-proteins while the large subunit is composed of 23S and 5S rRNAs, and more than 30 core r-proteins. Ribosome is not a stationary entity, rather it is adapted to changing environments giving rise to ribosome heterogeneity. Additionally, several small accessory proteins modulate the biogenesis, recycling, and function of the ribosome; many of these proteins and their molecular functions remain to be discovered. During protein synthesis, translational fidelity is maintained with high accuracy. However, the average translation error rate is relatively higher (10-4 to 10-3 per codon) compared to transcription or replication error rates. Maintaining proper translational fidelity requires cognate pairing of amino acids and tRNAs by aminoacyl-tRNA (aa-tRNA) synthetase and accurate decoding of mRNA codons by the corresponding aa- tRNAs on the ribosome. Several core and accessory r-proteins drive the correct decoding of the codons to maintain the translational fidelity. Various stress conditions such as nutritional and oxidative stresses often lead to mistranslation and growth defects in bacteria. We have recently identified several factors including a small conserved novel protein, SprV (90 amino acids), in Streptococcus mutans (an oral pathogen) that is required for translational fidelity, stress tolerance and adaptation. The major goal of this study is to understand at the molecular level how SprV and other factors such as EF-P and L9 (r- protein) modulate translational fidelity to alter cellular physiology of oral streptococci. PUBLIC HEALTH RELEVANCE: Translational fidelity during protein biosynthesis plays an important role during stress response and environmental adaptation in bacteria. The major goal of this project is to understand at the molecular level how some highly conserved novel proteins are involved in translational fidelity in oral streptococci. This study will broaden our overall understanding on the mechanisms of protein translation in streptococci and related organisms.