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Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle

Abstract

In eukaryotic cells, freshly synthesized messenger RNA (pre-mRNA) contains stretches of non-coding RNA that must be excised before the RNA can be translated into protein. Their removal is catalysed by the spliceosome, a large complex formed when a number of small nuclear ribonucleoprotein particles (snRNPs) bind sequentially to the pre-mRNA. The first snRNP to bind is called U1; other snRNPs (U2, U4/U6 and U5) follow1. Here we describe the three-dimensional structure of human U1 snRNP, determined by single-particle electron cryomicroscopy at 10 Å resolution. The reconstruction reveals a doughnut-shaped central element that accommodates the seven Sm proteins common to all snRNPs, supporting a proposed model of circular Sm protein arrangement2. By taking earlier biochemical results into account, we were able to assign the remaining density of the map to the other known components of U1 snRNP, deriving a structural model that describes the three-dimensional arrangement of proteins and RNA in U1 snRNP.

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Figure 1: The RNA and protein components of U1 snRNP.
Figure 2: Three-dimensional structure of human U1 snRNP at 10 Å resolution.
Figure 3: Modelling strategy: integration of available biochemical and structural information to fit the components of U1 snRNPs (Figs 1, 2a, b) into the three-dimensional electron cryomicroscopy maps.

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Acknowledgements

We thank F. Müller for the modelling software ERNA-3D; K. Nagai and C. Kambach for the Sm protein ring model; and M. Golas and B. Sander for assistance in electron microscopy. This work was supported by the Gottfried Wilhelm Leibniz Program and a grant from the Deutsche Forschungsgemeinschaft.

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Institut für Molekularbiologie und Tumorforschung, Emil-Mannkopfstrasse 2, 35037 Marburg, Germany

Max-Planck-Institut für biophysikalische Chemie, Am Fassberg 11, 37077Göttingen, Germany

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Stark, H., Dube, P., Lührmann, R. et al. Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle. Nature 409, 539–542 (2001). https://doi.org/10.1038/35054102

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