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Beckmann Lab - Research

Ribosome Biogenesis

Ribosome maturation is an extraordinary complex process that takes place mainly in the nucleolus of the cell and requires numerous additional protein factors. It is an ordered process that involves several steps of ribosomal RNA (rRNA) transcription, modification, folding and trimming followed by the regulated incorporation of ribosomal proteins.

In eukaryotes, this process is highly regulated, requiring large amounts of energy and many auxiliary factors. Most of the available knowledge so far is based on the yeast Saccharomyes cerevisiae, for which more than 200 auxiliary factors have been identified that interact transiently with the maturing ribosomal subunits (see figure; taken from Kressler et al., TIBS 2017).

After many years focusing on the biochemical characterization of pre-ribosomal particles, nowadays, one challenge of the field is to acquire structural and mechanistic information on the different steps taking place along the maturation path. Here, cryo-EM is particularly powerful, since this technique allows for the visualization of small amounts of native complexes and also facilitates classification of heterogeneous datasets originating from various sub-states.

To date, several pre-ribosomal particles have been structurally characterized in the Beckmann lab. Initially, the first native structure of a nucleoplasmic pre-60S intermediate was obtained. Next, the architecture of the following step, including the modifying Rix1-Rea1 machinery, was studied. Importantly, also the first structure of the elusive 90S pre-ribosome could be provided, a very early intermediate forming as soon as the rRNA is being transcribed for the 40S subunit. Taken together, this work provided already an overview of some key steps occurring during ribosome biogenesis. However, in order to achieve a more complete understanding of this process, and also of associated diseases in humans, more structures of biogenesis intermediates are required.