Cryo-EM structure of a human spliceosome activated for step 2 of splicing

Karl Bertram, Dmitry E. Agafonov, Wen-Ti Liu, Olexandr Dybkov, Cindy L. Will, Klaus Hartmuth, Henning Urlaub, Berthold Kastner (), Holger Stark () and Reinhard Lührmann ()
Additional contact information
Karl Bertram: MPI for Biophysical Chemistry
Dmitry E. Agafonov: MPI for Biophysical Chemistry
Wen-Ti Liu: MPI for Biophysical Chemistry
Olexandr Dybkov: MPI for Biophysical Chemistry
Cindy L. Will: MPI for Biophysical Chemistry
Klaus Hartmuth: MPI for Biophysical Chemistry
Henning Urlaub: Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry
Berthold Kastner: MPI for Biophysical Chemistry
Holger Stark: MPI for Biophysical Chemistry
Reinhard Lührmann: MPI for Biophysical Chemistry

Nature, 2017, vol. 542, issue 7641, 318-323

Abstract: Abstract Spliceosome rearrangements facilitated by RNA helicase PRP16 before catalytic step two of splicing are poorly understood. Here we report a 3D cryo-electron microscopy structure of the human spliceosomal C complex stalled directly after PRP16 action (C*). The architecture of the catalytic U2–U6 ribonucleoprotein (RNP) core of the human C* spliceosome is very similar to that of the yeast pre-Prp16 C complex. However, in C* the branched intron region is separated from the catalytic centre by approximately 20 Å, and its position close to the U6 small nuclear RNA ACAGA box is stabilized by interactions with the PRP8 RNase H-like and PRP17 WD40 domains. RNA helicase PRP22 is located about 100 Å from the catalytic centre, suggesting that it destabilizes the spliced mRNA after step two from a distance. Comparison of the structure of the yeast C and human C* complexes reveals numerous RNP rearrangements that are likely to be facilitated by PRP16, including a large-scale movement of the U2 small nuclear RNP.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/nature21079 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:542:y:2017:i:7641:d:10.1038_nature21079

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature21079

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().