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TitleMolecular architecture of the human U4/U6.U5 tri-snRNP.
Journal, issue, pagesScience, Vol. 351, Issue 6280, Page 1416-1420, Year 2016
Publish dateMar 25, 2016
AuthorsDmitry E Agafonov / Berthold Kastner / Olexandr Dybkov / Romina V Hofele / Wen-Ti Liu / Henning Urlaub / Reinhard Lührmann / Holger Stark /
PubMed AbstractThe U4/U6.U5 triple small nuclear ribonucleoprotein (tri-snRNP) is a major spliceosome building block. We obtained a three-dimensional structure of the 1.8-megadalton human tri-snRNP at a resolution ...The U4/U6.U5 triple small nuclear ribonucleoprotein (tri-snRNP) is a major spliceosome building block. We obtained a three-dimensional structure of the 1.8-megadalton human tri-snRNP at a resolution of 7 angstroms using single-particle cryo-electron microscopy (cryo-EM). We fit all known high-resolution structures of tri-snRNP components into the EM density map and validated them by protein cross-linking. Our model reveals how the spatial organization of Brr2 RNA helicase prevents premature U4/U6 RNA unwinding in isolated human tri-snRNPs and how the ubiquitin C-terminal hydrolase-like protein Sad1 likely tethers the helicase Brr2 to its preactivation position. Comparison of our model with cryo-EM three-dimensional structures of the Saccharomyces cerevisiae tri-snRNP and Schizosaccharomyces pombe spliceosome indicates that Brr2 undergoes a marked conformational change during spliceosome activation, and that the scaffolding protein Prp8 is also rearranged to accommodate the spliceosome's catalytic RNA network.
External linksScience / PubMed:26912367
MethodsEM (single particle)
Resolution7.0 Å
Structure data

6581

3jcr

EMDB-6581: 3D structure determination of the human *U4/U6.U5* tri-snRNP complex
PDB-3jcr: 3D structure determination of the human*U4/U6.U5* tri-snRNP complex
Method: EM (single particle) / Resolution: 7.0 Å

Source
  • homo sapiens (human)
KeywordsSPLICING / snRNP / spliceosome / human

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