Diverse ribosomes

Ribosome heterogeneity diversifies function in bacteria

The ribosome is not a monolith: individual ribosomes within a cell can differ from each other in their modification status, the riboosmal proteins they contain, and even the sequence of their ribosomal RNA. The Willi lab is on a mission to find out how these differences affect ribosome function, and how this benefits the bacterium.

RNA modifications. While oxidation of RNA is typically detrimental, E. coli surprisingly encodes a dedicated enzyme that adds a 5-hydroxyl-group to cytidine C2501 in close proximity the active site. We investigated this dynamic rRNA modification both in vivo through genetic manipulation, modification quantification, and from a mechanistic perspective through in vitro experiments. We found this modification to be highly dynamic and growth phase-dependent, with high oxidation levels helping E. coli adapt to oxidative stress. These findings provided first functional insights into the role of this unique rRNA modification and showcase a novel mechanism for how bacteria adapt to oxidative stress.

RNA sequence diversity. The E. coli genome encodes seven copies of the ribosomal RNAs 23S, 16S, and 5S. These copies are not identical; they differ in about 1.4% of their sequence. Do these small variations matter? Evidence from the Blanchard group suggests yes: in 2018 they showed that 16S rRNA variant H is an important regulator of the bacterium's stress response. This means that ribosome variation can directly affect how it functions. We set out to investigate these ribosomal differences further, and found that 23S rRNA variant A has higher protein yields than other variants. What's more, reducing the ribosome variety to only "A-type" ribosomes resulted in a highly active cell lysate, with the potential of boosting bio-production (patent filed). The Willi lab's latest project looks at ribosomal variants' sensitivity to antibiotics. We are actively investigating how these sequence differences could give infectious bacteria an edge in surviving treatment and developing antimicrobial resistance. This project is supported by funding from the Banting Research Foundation.