Molecular Shredder

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Artistic rendering of the superfluous RNA (red strands) being fed into the exoso

Artistic rendering of the superfluous RNA (red strands) being fed into the exosome ’shredder’ and broken down into individual RNA nucleotides. | Design: Anton Schmidt

Ribosomes are the protein factories of the cell. How they are assembled from subunits is a complicated and multi-layered process being investigated by a research team led by Ed Hurt at the Heidelberg University Biochemistry Center. Together with colleagues from Ludwig Maximilian University Munich, the researchers have now described the role that a type of molecular "shredder" plays in this process. The research results were published in the journal "Molecular Cell".

Ribosomes are giant molecules - a complex construct of special proteins and the hereditary material variant RNA. They are made up of two differently sized subunits assembled from precursor complexes known as pre-ribosomes. "The ribosomal RNA chains are also found in these precursors; initially the chains are connected but then need to separate to form the two subunits. The smaller of the two subunits peels itself out of its precursor complex, the 90S pre-ribosome," explains Prof. Hurt. The researchers have now been able to demonstrate how this onion-like peeling process is triggered by a molecular "shredder", the so-called RNA exosome.

According to Benjamin Lau, the first author on the paper, the RNA exosome positions itself precisely at a previously cut side of the precursor RNA, pulls out the superfluous RNA strand, and finally degrades it nucleotide by nucleotide. "To get rid of an overhanging tree branch in the backyard, you first cut it off and then feed it into the garden shredder," explains Benjamin Lau, who is a PhD candidate in Prof. Hurt’s research group. "In contrast, the RNA exosome positions itself directly on the cut open RNA strand end, acting there like a local shredder." Only then can the 90S pre-ribosome further develop into the small subunit.

B. Lau, J. Cheng, D. Flemming, G. La Venuta, O. Berninghausen, R. Beckmann, E. Hurt: Structure of the Maturing 90S Pre-ribosome in Association with the RNA Exosome, Molecular Cell 81(2): 293-303.e4 (2021)

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