Cryo-EM structure of the yeast U4/U6.U5 tri-snRNP at 3.7 Å resolution

Nature
Thi Hoang Duong NguyenKiyoshi Nagai

Abstract

U4/U6.U5 tri-snRNP represents a substantial part of the spliceosome before activation. A cryo-electron microscopy structure of Saccharomyces cerevisiae U4/U6.U5 tri-snRNP at 3.7 Å resolution led to an essentially complete atomic model comprising 30 proteins plus U4/U6 and U5 small nuclear RNAs (snRNAs). The structure reveals striking interweaving interactions of the protein and RNA components, including extended polypeptides penetrating into subunit interfaces. The invariant ACAGAGA sequence of U6 snRNA, which base-pairs with the 5'-splice site during catalytic activation, forms a hairpin stabilized by Dib1 and Prp8 while the adjacent nucleotides interact with the exon binding loop 1 of U5 snRNA. Snu114 harbours GTP, but its putative catalytic histidine is held away from the γ-phosphate by hydrogen bonding to a tyrosine in the amino-terminal domain of Prp8. Mutation of this histidine to alanine has no detectable effect on yeast growth. The structure provides important new insights into the spliceosome activation process leading to the formation of the catalytic centre.

References

Jan 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·T A Kunkel
Jan 1, 1994·Annual Review of Genetics·H D Madhani, C Guthrie
May 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·B LaggerbauerR Lührmann
Aug 26, 1998·Current Biology : CB·P L Raghunathan, C Guthrie
Feb 14, 2002·Nucleic Acids Research·Chun-Hong ChenSoo-Chen Cheng
Oct 11, 2002·The EMBO Journal·Stephanie NottrottReinhard Lührmann
Apr 15, 2003·Nature Structural Biology·Rene JørgensenGregers Rom Andersen
May 9, 2003·The Journal of Biological Chemistry·Cornelia BartelsPatrizia Fabrizio
Jun 5, 2003·Journal of Structural Biology·Joseph A Mindell, Nikolaus Grigorieff
Apr 21, 2004·Nature Structural & Molecular Biology·Daniel BoehringerHolger Stark
Mar 17, 2006·RNA·Tamara J Brenner, Christine Guthrie
May 13, 2006·Annual Review of Biophysics and Biomolecular Structure·Holger Stark, Reinhard Lührmann
Sep 12, 2006·Journal of Structural Biology·Thomas D GoddardThomas E Ferrin
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Melanie D OhiThomas Walz
Apr 5, 2008·Science·Navtej ToorAnna Marie Pyle
Jun 10, 2008·Nature Protocols·Sjors H W ScheresRoberto Marabini
Jun 19, 2009·The EMBO Journal·Elmar WolfReinhard Lührmann
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Mar 29, 2011·Cold Spring Harbor Perspectives in Biology·Cindy L Will, Reinhard Lührmann
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin
Jun 17, 2011·Annual Review of Biochemistry·Alfred Wittinghofer, Ingrid R Vetter
Nov 22, 2011·Journal of Molecular Biology·Sjors H W Scheres
Jul 31, 2012·Nature Methods·Sjors H W Scheres, Shaoxia Chen
Jan 29, 2013·Nature·Wojciech P GalejKiyoshi Nagai
Nov 8, 2013·Nature·Sebastian M FicaJoseph A Piccirilli
Nov 12, 2013·Nature Methods·Alp KucukelbirHemant D Tagare
Apr 22, 2014·Nature Structural & Molecular Biology·Sebastian M FicaJonathan P Staley

❮ Previous
Next ❯

Citations

Jun 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Matthias TheuserKarine F Santos
Jul 29, 2016·Wiley Interdisciplinary Reviews. RNA·Ruth Sperling
Aug 4, 2016·Nucleic Acids Research·Margaret L RodgersAaron A Hoskins
Aug 12, 2016·Nature·Brian Kosmyna, Charles C Query
Oct 25, 2016·Critical Reviews in Biochemistry and Molecular Biology·Noélia Custódio, Maria Carmo-Fonseca
Oct 30, 2016·Cell Cycle·Eva AbsmeierMarkus C Wahl
Apr 17, 2017·Methods : a Companion to Methods in Enzymology·Joseph Sperling, Ruth Sperling
Mar 21, 2017·Methods : a Companion to Methods in Enzymology·Andreas SchlundtMichael Sattler
Jan 4, 2017·Acta Crystallographica. Section D, Structural Biology·Eric J MontemayorSamuel E Butcher
May 23, 2017·Nature·Clemens PlaschkaKiyoshi Nagai
Jan 12, 2017·Nature·Sebastian M FicaKiyoshi Nagai
Jan 12, 2017·Nature·Karl BertramReinhard Lührmann
Mar 28, 2017·Current Opinion in Structural Biology·Dominika ElmlundHans Elmlund
Jan 26, 2018·RNA·Allison L DidychukDavid A Brow
Nov 18, 2017·Science·Shiheng LiuRui Zhao
Oct 6, 2017·Nature Structural & Molecular Biology·Sebastian M Fica, Kiyoshi Nagai
Mar 2, 2018·Annual Review of Biophysics·Max E WilkinsonKiyoshi Nagai
Jun 9, 2018·Nature Reviews. Drug Discovery·Jean-Paul RenaudChristian Wiesmann
Jul 4, 2018·Acta Crystallographica. Section D, Structural Biology·Andreas SchmittRalf Ficner
Aug 14, 2018·Wiley Interdisciplinary Reviews. RNA·Jorge Cruz-ReyesShelly Gulati
Sep 11, 2018·Acta Crystallographica. Section D, Structural Biology·Pavel V AfonineAlexandre Urzhumtsev
Nov 27, 2018·ELife·Claudia PellacaniMaria Patrizia Somma
Dec 7, 2018·Biomolecules·Caroline Rajiv, Tara L Davis
Mar 13, 2019·ELife·Basil J GreberEva Nogales
Feb 9, 2018·Nature·Linas UrnaviciusAndrew P Carter
Sep 8, 2016·Nature Medicine·Stanley Chun-Wei Lee, Omar Abdel-Wahab
Feb 16, 2019·Cold Spring Harbor Perspectives in Biology·Clemens PlaschkaKiyoshi Nagai
Sep 16, 2016·Nature·Rafael Fernandez-Leiro, Sjors H W Scheres
Jul 28, 2016·Nature·Wojciech P GalejKiyoshi Nagai
Aug 10, 2017·Nature Reviews. Molecular Cell Biology·Lydia HerzelKarla M Neugebauer
Aug 27, 2016·Science·Reinhard RauhutReinhard Lührmann
Sep 28, 2017·Nature Reviews. Molecular Cell Biology·Yigong Shi
Oct 11, 2019·PLoS Biology·Cathleen M GreenMarlene Belfort
Jul 16, 2019·Human Molecular Genetics·Katherine A WoodRaymond T O'Keefe
Mar 26, 2016·Science·Jamie H D Cate
Jul 23, 2016·Science·Chuangye YanYigong Shi

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPases
GTPase
two-hybrid

Software Mentioned

Xmipp
REFMAC
Pymol
CTFFIND4
Chimera
ILS
Resmap
MOTIONCORR
PROSMART

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.