Three-dimensional structure of the native spliceosome by cryo-electron microscopy

Molecular Cell
Maia AzubelRuth Sperling

Abstract

Splicing of pre-mRNA occurs in a multicomponent macromolecular machine--the spliceosome. The spliceosome can be assembled in vitro by a stepwise assembly of a number of snRNPs and additional proteins on exogenously added pre-mRNA. In contrast, splicing in vivo occurs in preformed particles where endogenous pre-mRNAs are packaged with all five spliceosomal U snRNPs (penta-snRNP) together with other splicing factors. Here we present a three-dimensional image reconstruction by cryo-electron microscopy of native spliceosomes, derived from cell nuclei, at a resolution of 20 angstroms. The structure revealed an elongated globular particle made up of two distinct subunits connected to each other leaving a tunnel in between. We show here that the larger subunit is a suitable candidate to accommodate the penta-snRNP, and that the tunnel could accommodate the pre-mRNA component of the spliceosome. The features this structure reveals provide new insight into the global architecture of the native splicing machine.

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Citations

Mar 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·Lily AgranatRuth Sperling
Mar 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Deborah F KellyThomas Walz
Jun 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Eyal KamhiJoseph Sperling
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Feb 13, 2009·Current Opinion in Structural Biology·Reinhard Lührmann, Holger Stark

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