A hyperactive mutant of the RNA polymerase dedicated to ribosome synthesis

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Ribosomes are, within the cells, the bodies responsible for the production of proteins. They are composed of an assembly of molecules including’RNA polymerase I, an enzyme specifically responsible for the synthesis of RNA components. Researchers have managed to isolate a mutant polymerase that is more active than the normal enzyme. The existence of this «super-enzyme» producing more RNA sheds light on the biogenesis carried out in ribosomes and could constitute a primary target for certain cancers. These results, published in the journal PLoS Genetics, have notably used a MeTi speciality, namely the single-molecule approach using electron microscopy.

Capture of a Miller tree, also known as a Christmas tree because of their shape. The «trunk» of these trees is a DNA molecule, the «baubles» are various proteins, and the beads connecting the branches to the trunk are RNAs. Counting the «baubles» makes it possible to quantify protein production. Photo: MeTI

An open conformation, allowing the insertion of the template DNA into the catalytic centre (left), alternates with a closed conformation capable of maintaining the efficient capture of the short elongating DNA (right). Super-active mutants of RNA polymerase I (red on the central model) increase the enzyme's activity by facilitating the structural rearrangements necessary for the transition between these two forms (blue, yellow and red arrows).

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Contact: Olivier Gadal
Publication references : Genetic analyses led to the discovery of a super-active mutant of RNA polymerase I. Darrière T, Pilsl M, Sarthou MK, Chauvier A, Genty T, Audibert S, Dez C, Léger-Silvestre I, Normand C, Henras AK, Kwapisz M, Calvo O, Fernández-Tornero C, Tschochner H, Gadal O. PLoS Genet. 2019 May 28;15(5):e1008157.

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