On Thursday, 12.12.2019, 5.15 pm
Boris Görke (Max-Perutz-Labs, Wien), will give an SFB 902 lecture:
„A regulatory network controlling bacterial cell envelope synthesis at the post-transcriptional level“.
Venue: TU Darmstadt, Campus Botanischer Garten, lecture hall: B101/52
Guests are welcome!
Gram-negative bacteria such as E. coli possess a cell envelope consisting of peptidoglycan and an outer membrane, which provides protection against environmental stresses. Synthesis of glucosamine-6-phosphate (GlcN6P) by enzyme GlmS represents the first and rate-limiting step in the cell envelope synthesis pathway. In order to ensure continuous cell envelope synthesis, GlcN6P homeostasis is required, which is achieved through a post-transcriptional regulatory circuit composed of small RNAs (sRNAs) GlmY and GlmZ and the RNA-binding protein RapZ. GlmZ activates glmS translation by base-pairing. When GlcN6P is ample, GlmZ is bound by adaptor protein RapZ and inactivated by cleavage through recruitment of RNase E. Decreasing GlcN6P concentrations provoke accumulation of the homologous sRNA GlmY, which acts as decoy and sequesters RapZ thereby counteracting GlmZ decay. The crystal structure of RapZ revealed a novel type of RNA-binding protein, which putatively evolved from re-purpose of a glycolytic enzyme. The active form of RapZ corresponds to a tetramer, which may activate the likewise tetrameric RNase E in an encounter complex to cleave sRNA GlmZ that is presumably sandwiched between the two tetramers. Notably, RapZ also represents the sought GlcN6P sensor: RapZ binds GlcN6P with high affinity and rapZ mutants are blind for this metabolite. Upon GlcN6P depletion, RapZ stimulates a transcription factor through interaction to increase GlmY expression levels. Thus, RapZ has a moonlighting function and controls production of its own decoy GlmY, which subsequently sequesters the available RapZ protein into long-lived ribonucleoprotein complexes, thereby counteracting GlmZ decay.