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The architecture of the spliceosomal U4/U6.U5 tri-snRNP

U4/U6.U5 tri-snRNP is a 1.5 MDa pre-assembled spliceosomal complex comprising U5 snRNA, extensively base-paired U4/U6 snRNAs and >30 proteins, including the key components Prp8, Brr2 and Snu114. The tri-snRNP combines with a pre-mRNA substrate bound to U1 and U2 snRNPs and transforms into a catal...

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Autores principales: Nguyen, Thi Hoang Duong, Galej, Wojciech P., Bai, Xiao-chen, Savva, Christos G., Newman, Andrew J., Scheres, Sjors H. W., Nagai, Kiyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536768/
https://www.ncbi.nlm.nih.gov/pubmed/26106855
http://dx.doi.org/10.1038/nature14548
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author Nguyen, Thi Hoang Duong
Galej, Wojciech P.
Bai, Xiao-chen
Savva, Christos G.
Newman, Andrew J.
Scheres, Sjors H. W.
Nagai, Kiyoshi
author_facet Nguyen, Thi Hoang Duong
Galej, Wojciech P.
Bai, Xiao-chen
Savva, Christos G.
Newman, Andrew J.
Scheres, Sjors H. W.
Nagai, Kiyoshi
author_sort Nguyen, Thi Hoang Duong
collection PubMed
description U4/U6.U5 tri-snRNP is a 1.5 MDa pre-assembled spliceosomal complex comprising U5 snRNA, extensively base-paired U4/U6 snRNAs and >30 proteins, including the key components Prp8, Brr2 and Snu114. The tri-snRNP combines with a pre-mRNA substrate bound to U1 and U2 snRNPs and transforms into a catalytically active spliceosome following extensive compositional and conformational changes triggered by unwinding of the U4/U6 snRNAs. CryoEM single-particle reconstruction of yeast tri-snRNP at 5.9Å resolution reveals the essentially complete organization of its RNA and protein components. The single-stranded region of U4 snRNA between its 3′-stem-loop and the U4/U6 snRNA stem I is loaded into the Brr2 helicase active site ready for unwinding. Snu114 and the N-terminal domain of Prp8 position U5 snRNA to insert its Loop I, which aligns the exons for splicing, into the Prp8 active site cavity. The structure provides crucial insights into the activation process and the active site of the spliceosome.
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spelling pubmed-45367682016-01-02 The architecture of the spliceosomal U4/U6.U5 tri-snRNP Nguyen, Thi Hoang Duong Galej, Wojciech P. Bai, Xiao-chen Savva, Christos G. Newman, Andrew J. Scheres, Sjors H. W. Nagai, Kiyoshi Nature Article U4/U6.U5 tri-snRNP is a 1.5 MDa pre-assembled spliceosomal complex comprising U5 snRNA, extensively base-paired U4/U6 snRNAs and >30 proteins, including the key components Prp8, Brr2 and Snu114. The tri-snRNP combines with a pre-mRNA substrate bound to U1 and U2 snRNPs and transforms into a catalytically active spliceosome following extensive compositional and conformational changes triggered by unwinding of the U4/U6 snRNAs. CryoEM single-particle reconstruction of yeast tri-snRNP at 5.9Å resolution reveals the essentially complete organization of its RNA and protein components. The single-stranded region of U4 snRNA between its 3′-stem-loop and the U4/U6 snRNA stem I is loaded into the Brr2 helicase active site ready for unwinding. Snu114 and the N-terminal domain of Prp8 position U5 snRNA to insert its Loop I, which aligns the exons for splicing, into the Prp8 active site cavity. The structure provides crucial insights into the activation process and the active site of the spliceosome. 2015-06-24 2015-07-02 /pmc/articles/PMC4536768/ /pubmed/26106855 http://dx.doi.org/10.1038/nature14548 Text en Reprints and permissions information is available at www.nature.com/reprints (http://www.nature.com/reprints) . Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Nguyen, Thi Hoang Duong
Galej, Wojciech P.
Bai, Xiao-chen
Savva, Christos G.
Newman, Andrew J.
Scheres, Sjors H. W.
Nagai, Kiyoshi
The architecture of the spliceosomal U4/U6.U5 tri-snRNP
title The architecture of the spliceosomal U4/U6.U5 tri-snRNP
title_full The architecture of the spliceosomal U4/U6.U5 tri-snRNP
title_fullStr The architecture of the spliceosomal U4/U6.U5 tri-snRNP
title_full_unstemmed The architecture of the spliceosomal U4/U6.U5 tri-snRNP
title_short The architecture of the spliceosomal U4/U6.U5 tri-snRNP
title_sort architecture of the spliceosomal u4/u6.u5 tri-snrnp
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536768/
https://www.ncbi.nlm.nih.gov/pubmed/26106855
http://dx.doi.org/10.1038/nature14548
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