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

Thi Hoang Duong Nguyen, Wojciech P. Galej, Xiao Chen Bai, Chris Oubridge, Andrew J. Newman, Sjors H.W. Scheres, Kiyoshi Nagai

Research output: Contribution to journalArticle

117 Citations (Scopus)

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 Î 3-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.

Original languageEnglish (US)
Pages (from-to)298-302
Number of pages5
JournalNature
Volume530
Issue number7590
DOIs
StatePublished - Feb 18 2016

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U5 Small Nuclear Ribonucleoproteins
Spliceosomes
Histidine
Yeasts
Cryoelectron Microscopy
RNA Splice Sites
Hydrogen Bonding
Guanosine Triphosphate
Base Pairing
Alanine
Saccharomyces cerevisiae
Tyrosine
Exons
Proteins
Nucleotides
Phosphates
RNA
Peptides
Mutation
Growth

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Nguyen, T. H. D., Galej, W. P., Bai, X. C., Oubridge, C., Newman, A. J., Scheres, S. H. W., & Nagai, K. (2016). Cryo-EM structure of the yeast U4/U6.U5 tri-snRNP at 3.7 Å resolution. Nature, 530(7590), 298-302. https://doi.org/10.1038/nature16940

Cryo-EM structure of the yeast U4/U6.U5 tri-snRNP at 3.7 Å resolution. / Nguyen, Thi Hoang Duong; Galej, Wojciech P.; Bai, Xiao Chen; Oubridge, Chris; Newman, Andrew J.; Scheres, Sjors H.W.; Nagai, Kiyoshi.

In: Nature, Vol. 530, No. 7590, 18.02.2016, p. 298-302.

Research output: Contribution to journalArticle

Nguyen, THD, Galej, WP, Bai, XC, Oubridge, C, Newman, AJ, Scheres, SHW & Nagai, K 2016, 'Cryo-EM structure of the yeast U4/U6.U5 tri-snRNP at 3.7 Å resolution', Nature, vol. 530, no. 7590, pp. 298-302. https://doi.org/10.1038/nature16940
Nguyen THD, Galej WP, Bai XC, Oubridge C, Newman AJ, Scheres SHW et al. Cryo-EM structure of the yeast U4/U6.U5 tri-snRNP at 3.7 Å resolution. Nature. 2016 Feb 18;530(7590):298-302. https://doi.org/10.1038/nature16940
Nguyen, Thi Hoang Duong ; Galej, Wojciech P. ; Bai, Xiao Chen ; Oubridge, Chris ; Newman, Andrew J. ; Scheres, Sjors H.W. ; Nagai, Kiyoshi. / Cryo-EM structure of the yeast U4/U6.U5 tri-snRNP at 3.7 Å resolution. In: Nature. 2016 ; Vol. 530, No. 7590. pp. 298-302.
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