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TitleStructural insights into human exon-defined spliceosome prior to activation.
Journal, issue, pagesCell Res, Year 2024
Publish dateApr 24, 2024
AuthorsWenyu Zhang / Xiaofeng Zhang / Xiechao Zhan / Rui Bai / Jianlin Lei / Chuangye Yan / Yigong Shi /
PubMed AbstractSpliceosome is often assembled across an exon and undergoes rearrangement to span a neighboring intron. Most states of the intron-defined spliceosome have been structurally characterized. However, ...Spliceosome is often assembled across an exon and undergoes rearrangement to span a neighboring intron. Most states of the intron-defined spliceosome have been structurally characterized. However, the structure of a fully assembled exon-defined spliceosome remains at large. During spliceosome assembly, the pre-catalytic state (B complex) is converted from its precursor (pre-B complex). Here we report atomic structures of the exon-defined human spliceosome in four sequential states: mature pre-B, late pre-B, early B, and mature B. In the previously unknown late pre-B state, U1 snRNP is already released but the remaining proteins are still in the pre-B state; unexpectedly, the RNAs are in the B state, with U6 snRNA forming a duplex with 5'-splice site and U5 snRNA recognizing the 3'-end of the exon. In the early and mature B complexes, the B-specific factors are stepwise recruited and specifically recognize the exon 3'-region. Our study reveals key insights into the assembly of the exon-defined spliceosomes and identifies mechanistic steps of the pre-B-to-B transition.
External linksCell Res / PubMed:38658629
MethodsEM (single particle)
Resolution2.6 - 3.25 Å
Structure data

34500

8h6e

EMDB-34500, PDB-8h6e:
Cryo-EM structure of human exon-defined spliceosome in the late pre-B state.
Method: EM (single particle) / Resolution: 3.2 Å

34505

8h6j

EMDB-34505, PDB-8h6j:
Cryo-EM structure of human exon-defined spliceosome in the mature pre-B state.
Method: EM (single particle) / Resolution: 3.25 Å

34507

8h6k

EMDB-34507, PDB-8h6k:
Cryo-EM structure of human exon-defined spliceosome in the mature B state.
Method: EM (single particle) / Resolution: 2.7 Å

34508

8h6l

EMDB-34508, PDB-8h6l:
Cryo-EM structure of human exon-defined spliceosome in the early B state.
Method: EM (single particle) / Resolution: 2.6 Å

Chemicals

ChemComp-IHP:
INOSITOL HEXAKISPHOSPHATE / Phytic acid

ChemComp-MG:
Unknown entry

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM / Guanosine triphosphate

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
KeywordsSPLICING / exon-defined spliceosome / late pre-B state / RNA splicing / Post pre-B state

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