Structure of the human activated spliceosome in three conformational states

  title={Structure of the human activated spliceosome in three conformational states},
  author={Xiaofeng Zhang and Chuangye Yan and Xiechao Zhan and Lijia Li and Jianlin Lei and Yigong Shi},
  journal={Cell Research},
  pages={307 - 322}
During each cycle of pre-mRNA splicing, the pre-catalytic spliceosome (B complex) is converted into the activated spliceosome (Bact complex), which has a well-formed active site but cannot proceed to the branching reaction. Here, we present the cryo-EM structure of the human Bact complex in three distinct conformational states. The EM map allows atomic modeling of nearly all protein components of the U2 small nuclear ribonucleoprotein (snRNP), including three of the SF3a complex and seven of… 

Structures of the human spliceosomes before and after release of the ligated exon

Cryo-electron microscopy structures of the human post-catalytic spliceosome (P complex) and intron lariat spliceoome (ILS) at average resolutions of 3.0 and 2.9 Å are reported, revealing mechanistic insights into exon release and splicedosome disassembly.

Structures of the human pre-catalytic spliceosome and its precursor spliceosome

Cryo-electron microscopy structures of the human pre-B complex and the human B complex are reported and mechanistic insights into the assembly and activation of thehuman spliceosome are revealed.

Structures of the Catalytically Activated Yeast Spliceosome Reveal the Mechanism of Branching

This analysis reveals the functional mechanism of Yju2 and Cwc25 in branching and constitutes compelling evidence for substrate-specific conformations of the spliceosome in a major functional state.

Smu1 and RED play an important role for the activation of human spliceosomes

The results indicate that defects in splicing triggered by the absence of Smu1 and RED were caused by impaired spliceosome activation, and suggest that Smu and RED are important for splicing in general, and thus not only involved in the regulation of alternative splicing.

Molecular Mechanisms of pre-mRNA Splicing through Structural Biology of the Spliceosome.

The spliceosome is a protein-directed metalloribozyme, driven by the RNA-dependent ATPase/helicases, resulting in the recruitment and dissociation of specific splicing factors that enable the reaction.

Molecular architecture of the human 17S U2 snRNP

The cryo-EM structure of human U2 small nuclear ribonucleoprotein (snRNP) offers insights into what rearrangements are required for this snRNP to be stably incorporated into the spliceosome, and the role that the DEAD-box ATPase PRP5 may have in these rearrangement.

Structural dynamics of the N-terminal domain and the Switch loop of Prp8 during spliceosome assembly and activation

The structural dynamics of two elements of Prp8, the N-terminal domain (N-domain) and the Switch loop, are reviewed, and the dynamic organisation and underlying functional significance of these two elements during spliceosome assembly and activation are delineated.

Structure of the activated human minor spliceosome

Structural comparison between the major and minorspliceosomes may reveal valuable information on protein components specific to either spliceosome, U12-type intron recognition, snRNA conformation, active site configuration, and regulatory mechanisms.

Structural Basis of Nuclear pre-mRNA Splicing: Lessons from Yeast.

The structures show how a single RNA catalytic center forms during activation and accomplishes both steps of the splicing reaction, and reveal how spliceosomal helicases remodel thespliceosome for active site formation, substrate docking, reaction product undocking, and splicedosome disassembly.

Structural insights into how Prp5 proofreads the pre-mRNA branch site

The data suggest that binding of Hsh155HEAT to the bulged BS-A of the U2-BS helix triggers closure of Hhsh155 HEAT, which in turn destabilizes Prp5 binding, hindering spliceosome assembly if branch-site mutations prevent the remodelling of H Sh 155HEAT.



Crystal structure of a core spliceosomal protein interface

The 2.5-Å crystal structure of a complex containing p14 and a peptide derived from the p14-associated U2 snRNP component SF3b 155 suggests that p14·SF3b155 presents a noncanonical surface for RNA recognition at the heart of the mammalian spliceosome.

Structure of a yeast activated spliceosome at 3.5 Å resolution

An atomic structure of an activated spliceosome from Saccharomyces cerevisiae, known as the Bact complex, determined by cryo–electron microscopy at an average resolution of 3.52 angstroms is reported, which outlines a molecular framework for the pre-mRNA splicing reaction.

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

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.

The Spliceosome: A Protein-Directed Metalloribozyme.

  • Yigong Shi
  • Biology, Chemistry
    Journal of molecular biology
  • 2017

Structure of a yeast step II catalytically activated spliceosome

A high-resolution structure of the step II catalytically activated spliceosome (the C* complex) from Saccharomyces cerevisiae is reported, which shows conformational changes that position catalytic motifs to accomplish the second splicing reaction.

Structure of a human catalytic step I spliceosome

Cryo–electron microscopy structure of the human C complex spliceosome reveals mechanistic insights into ribonucleoprotein remodeling and allows the proposition of a working mechanism for the C-to-C* transition.

Cooperative structure of the heterotrimeric pre-mRNA retention and splicing complex

The solution NMR structure of the RES core complex from Saccharomyces cerevisiae shows an intricate folding of three components that stabilizes the RNA-recognition motif (RRM) fold of Snu17p and increases binding affinity in tertiary interactions between the components by more than 100-fold compared to that in binary interactions.

Structure of a yeast catalytic step I spliceosome at 3.4 Å resolution

An atomic structure of a catalytic step I spliceosome from Saccharomyces cerevisiae, as determined by cryo–electron microscopy at an average resolution of 3.4 angstroms is reported, representing the conformation of the splicesome after the first-step reaction.

Structure of a pre-catalytic spliceosome

The cryo-electron microscopy structure of the yeast Saccharomyces cerevisiae pre-catalytic B complex spliceosome at near-atomic resolution is reported, providing important insights into the events leading to active site formation.