Genetics, Epigenetics & Gene Regulation
Ribosome Heterogeneity in Bacteria
isabella.moll [AT] univie.ac [DOT] at
Dr. Bohr-Gasse 9, 1030 Vienna | Room: 4.028
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...more
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 70SΔ43 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 16SΔ43 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.close
Temmel, Hannes; Müller, Christian; Sauert, Martina; Vesper, Oliver; Reiss, Ariela; Popow, Johannes; Martinez, Javier; Moll, Isabella (2017). The RNA ligase RtcB reverses MazF-induced ribosome heterogeneity in Escherichia coli. NUCLEIC ACIDS RES;8(45):4708-4721. PMID: 27789694
Sauert, Martina; Wolfinger, Michael T; Vesper, Oliver; Müller, Christian; Byrgazov, Konstantin; Moll, Isabella (2016). The MazF-regulon: a toolbox for the post-transcriptional stress response in Escherichia coli. NUCLEIC ACIDS RES. PMID: 26908653
Vesper, Oliver; Amitai, Shahar; Belitsky, Maria; Byrgazov, Konstantin; Kaberdina, Anna Chao; Engelberg-Kulka, Hanna; Moll, Isabella (2011). Selective Translation of Leaderless mRNAs by Specialized Ribosomes Generated by MazF in Escherichia coli. CELL(147):147-57. PMID: 21944167
Doctoral Program "RNA Biology"
The Group Moll participates in the special Doctoral Program "RNA Biology" reviewed and funded by the Austrian Research Fund FWF.
SFB RNA-Reg - RNA regulation of the transcriptome
The Group Moll participates in the Special Research Area (SFB) "RNA-Reg - RNA regulation of the transcriptome" funded by the Austrian Science Fund FWF. SFB's are peer-reviewed, highly interactive research networks, established to foster long-term, interdisciplinary co-operation of local research groups working on the frontiers of their thematic areas.