Moll

One of the most intricate and fundamental processes of life is the translation of the genetic code into proteins. Decoding mRNA-based information into the corresponding sequence of amino acids is performed by a complex ribonucleoprotein particle, the ribosome. Traditionally, the ribosome is viewed as highly conserved machinery with an invariable RNA and protein complement. This perception of invariance has been

One of the most intricate and fundamental processes of life is the translation of the genetic code into proteins. Decoding mRNA-based information into the corresponding sequence of amino acids is performed by a complex ribonucleoprotein particle, the ribosome. Traditionally, the ribosome is viewed as highly conserved machinery with an invariable RNA and protein complement. This perception of invariance has been perpetuated by the determination of high resolution structures, which implied that ribosomes are homogeneous entities that are not considered to have an intrinsic regulatory capacity.

In my group we aim to challenge this assumption and to decipher mechanisms in bacteria that modulate the translational program by ribosome heterogeneity. In particular, we focus on modifications of ribosomal RNAs and proteins that alter ribosome specificity in response to a variety of stress conditions.

We have shown that the selectivity of the translational machinery can be efficiently adapted to environmental conditions by the stress-activated endoribonuclease MazF and the RNA ligase RtcB. During stress active MazF, the toxin component of the toxin-antitoxin module mazEF, specifically removes the 3´-terminal 16S rRNA fragment of 43 nucleotides in length (RNA43) (Vesper et al., 2011). As this fragment comprises the anti-Shine-Dalgarno sequence that is vital for translation initiation on canonical mRNAs, the resulting 70S^Δ43 ribosomes selectively translate mRNAs that are likewise processed by MazF within their 5’-untranslated region (Sauert et al., 2016). Surprisingly, our results further reveal that this this `one-step mechanism´ of ribosome specialization is reversible. The RNA ligase RtcB recovers the subpopulation of heterogeneous ribosomes by re-ligation of the 16S^Δ43 rRNA with the stable RNA43 thereby restoring their proficiency to translate canonical mRNAs (Temmel et al., 2016). Taken together, the antagonizing factors MazF and RtcB provide a flexible and energy-efficient link between the number of specialized ribosomes and changing environmental conditions. Since the bacterial cells are constantly equipped with these factors, this balancing mechanism ensures an immediate and almost reflexive response to external stimuli, what is in stark contrast to the time-consuming transcriptional stress response.

Collectively, our studies introduce the mechanism of reversible ribosome heterogeneity as a novel concept for post-transcriptional regulation in bacteria and raise the translational apparatus from a cellular factory required to make proteins to a central control unit in gene expression.