Seminar

Dynamics aspects of translation initiation and its control in bacteria with evolutionary considerations

Stefano Marzi, PhD

In bacteria, translational control plays a central role in adaptive processes such as stress responses and virulence. Regulation is often exerted at the earliest step of translation, the initiation process, when the mRNA is recruited on the small ribosomal subunit and is correctly positioned in the decoding channel for tRNA interaction. Structured 5’ untranslated (UTR) regions of mRNAs play multiple functions in translational control because they can influence the kinetics of initiation complex formation and their structures respond directly to physical (T°C, pH) or to trans-acting factors (metabolites, non-coding RNAs or proteins). We have recently demonstrated that, in the Gram-negative bacterium Escherichia coli, the ribosomal protein S1 (EcoS1) endows the 30S subunit with an RNA chaperone activity that allows dealing with a huge variety of mRNA structures. With its six OB folds RNA binding domains, EcoS1 anchors the mRNAs on the ribosome and unfolds their structure to accommodate them in the decoding channel (1). In addition to its essential role in translation, S1 on the ribosome is also involved in other functions important for the cellular RNA metabolism. While its first 4 OB-fold domains retain all the translation activities, its two last C-terminal domains contribute to RNA maturation and stress responses. In order to obtain an evolutionary view of translation initiation and its regulation, we are now studying translation initiation in the Gram-positive opportunistic pathogen Staphylococcus aureus. E. coli and S. aureus have diverged 107 years ago and their translation initiation processes show significant differences in their ability to cope with structured mRNAs. Recently, we have demonstrated that purified staphylococcal 30S subunits do not contain S1 and are not able to efficiently form initiation complexes with natural S. aureus structured mRNAs (2, 3). Interestingly, we have shown that purified S. aureus S1 (SauS1) is able to stimulate the translation initiation of structured mRNAs most probably through direct interaction with the mRNAs. In fact, SauS1 can form different cellular complexes involved in non-coding RNA-dependent regulation and in RNA maturation/degradation. (1) Duval M, Korepanov A, Fuchsbauer O, Fechter P, Haller A, Fabbretti A, Choulier L, Micura R, Klaholz BP, Romby P, Springer M, and Marzi S. Escherichia coli ribosomal protein S1 unfolds structured mRNAs onto the ribosome for active translation initiation. PLoS Biology 2013 Dec;11(12):e1001731. doi: 10.1371/journal.pbio.1001731. Epub 2013 Dec 10. (2) Khusainov I, Vicens Q, Bochler A, Grosse F, Myasnikov A, Menetret JF, Chicher J, Marzi S, Romby P, Yusupova G, Yusupov M, and Hashem Y. Structure of the 70S ribosome from human pathogen Staphylococcus aureus. Nucleic Acids Research 2016 44: 10491-10504. (3) Khusainov I, Marenna A, Cerciat M, Fechter P, Hashem Y, Marzi S, Romby P, Yusupova G, and Yusupov M. A glimpse on Staphylococcus aureus translation machinery and i