Roles of elusive translational GTPases come to light and inform on the process of ribosome biogenesis in bacteria

Abstract

Summary Protein synthesis relies on several translational GTPases (trGTPases), related proteins that couple the hydrolysis of GTP to specific molecular events on the ribosome. Most bacterial trGTPases, including IF2, EF‐Tu, EF‐G and RF3, play well‐known roles in translation. The cellular functions of LepA (also termed EF4) and BipA (also termed TypA), conversely, have remained enigmatic. Recent studies provide compelling in vivo evidence that LepA and BipA function in biogenesis of the 30S and 50S subunit respectively. These findings have important implications for ribosome biogenesis in bacteria. Because the GTPase activity of each of these proteins depends on interactions with both ribosomal subunits, some portion of 30S and 50S assembly must occur in the context of the 70S ribosome. In this review, we introduce the trGTPases of bacteria, describe the new functional data on LepA and BipA, and discuss the how these findings shape our current view of ribosome biogenesis in bacteria.

A temperature-dependent translational switch controls biofilm development inVibrio cholerae

“…To explain this, it has been proposed that BipA together with ppGpp controls ribosome binding specificity to regulate the synthesis of virulence or stress factors 40 . However, other studies suggest that BipA is important for biogenesis of the 50S 49,51,52 . Contrary to the cold sensitive phenotype of E. coli bipA mutant 44 , growth of V. cholerae co969 Δ bipA was not affected at 22°C (SM Figure 3), suggesting that impact of BipA on biofilm formation is more likely due to a re-organization of ribosomal translation specificity rather than a general defect in ribosome assembly and protein synthesis.…”

“…As BipA is a ribosome assembly factor at low temperatures 47,49 , we wondered if it exerted a global effect on translation along with its role in controlling biofilm formation. To address this question, we performed global proteomic analyses of co969 WT and Δ bipA grown at either 37°C (rugose colonies) or at 22°C (smooth colonies), followed by 4 comparative analyses: (i) WT vs Δ bipA at 37°C; (ii) WT vs Δ bipA at 22°C colonies; (iii) WT 37°C vs 22°C colonies; and (iv) Δ bipA 37°C vs 22°C colonies.…”

“…BipA is thought to act as a ribosome assembly factor 47,50,49 that modulates translation of a specific and distinct subset of mRNAs under specific stress conditions 50 . To explain this, it has been proposed that BipA together with ppGpp controls ribosome binding specificity to regulate the synthesis of virulence or stress factors 40 .…”

“…Since BipA is highly conserved amongst bacteria 36,37,49 it is tempting to speculate that the BipA-dependent control of biofilm formation by temperature observed in V. cholerae could be conserved in other bacteria. In agreement with this hypothesis, deletion of BipA has been associated to increased biofilm levels in P. aeruginosa PAO1 41 and Bordetella holmesii 45 .…”

The enigmatic ribosomal stalk

“…EF4 and BipA are paralogs of EF-G, but among other differences, they lack the G ′ domain. For further structural and functional comparisons see Liljas and Ehrenberg (2013); Heller et al (2017); Gibbs and Fredrick (2018).…”