High-resolution photograph of the enzyme that synthesizes the ribosome

High-resolution photograph of the enzyme that synthesizes the ribosome

The team led by Carlos Fernández Tornero at the Biological Research Center of CSIC has determined the three-dimensional structure of RNA polymerase I (Pol I), the giant enzyme responsible for producing the RNA that will eventually form the ribosome in eukaryotic cells. The work, published as a full article in the latest issue of Nature, opens the door to finding new antitumor drugs.

Pol I is a 14-protein complex that synthesizes the core of the ribosome, the molecular machine that makes proteins within the cell. Since the ribosome represent between 15% and 20% of the cell weight, the activity of Pol I can reach 60% of cellular RNA synthesis to produce approximately 2,000 ribosomes per minute. Defects in Pol I regulation are associated with alterations in cellular proliferation and, thus, with tumour development.

Scientists have obtained the atomic structure of Pol I in the latent state, i.e. before transcription starts, which has revealed features never seen in other Pol enzymes. For example, Pol I incorporates modules that must be recruited in other Pols, which could explain why this enzyme is faster than their counterparts. As there is no need to recruit external factors, things are simpler. In principle this means less control on the enzyme activity, but Pol I has developed a self-regulating mechanism that blocks its DNA binding site when this function is not required.

Given the large size and dynamism of this complex enzyme, advanced methods for crystallization and structure determination through X-ray crystallography were required. Major contributions to this 10-year effort were performed by Nicholas Taylor and Federico Ruiz from the aforementioned CIB team, in collaboration with Maria Moreno Morcillo and Christoph Müller at EMBL Heidelberg, as well as scientists from the University of Göttingen and the Soleil synchrotron in Paris.

Carlos Fernández-Tornero, María Moreno-Morcillo, Umar J. Rashid, Nicholas M. I. Taylor, Federico M. Ruiz, Tim Gruene, Pierre Legrand, Ulrich Steuerwald y Christoph W. Müller. Crystal structure of the 14-subunit RNA polymerase I. Nature. DOI: 10.1038/nature12636