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Structure paper

TitleStructural basis of 5' splice site recognition by the minor spliceosome.
Journal, issue, pagesMol Cell, Vol. 85, Issue 3, Page 652-664.e4, Year 2025
Publish dateFeb 6, 2025
AuthorsJiangfeng Zhao / Daniel Peter / Irina Brandina / Xiangyang Liu / Wojciech P Galej /
PubMed AbstractThe minor spliceosome catalyzes excision of U12-dependent introns from precursors of eukaryotic messenger RNAs (pre-mRNAs). This process is critical for many cellular functions, but the underlying ...The minor spliceosome catalyzes excision of U12-dependent introns from precursors of eukaryotic messenger RNAs (pre-mRNAs). This process is critical for many cellular functions, but the underlying molecular mechanisms remain elusive. Here, we report a cryoelectron microscopy (cryo-EM) reconstruction of the 13-subunit human U11 small nuclear ribonucleoprotein particle (snRNP) complex in apo and substrate-bound forms, revealing the architecture of the U11 small nuclear RNA (snRNA), five minor spliceosome-specific factors, and the mechanism of the U12-type 5' splice site (5'SS) recognition. SNRNP25 and SNRNP35 specifically recognize U11 snRNA, while PDCD7 bridges SNRNP25 and SNRNP48, located at the distal ends of the particle. SNRNP48 and ZMAT5 are positioned near the 5' end of U11 snRNA and stabilize binding of the incoming 5'SS. Recognition of the U12-type 5'SS is achieved through base-pairing to the 5' end of the U11 snRNA and unexpected, non-canonical base-triple interactions with the U11 snRNA stem-loop 3. Our structures provide mechanistic insights into U12-dependent intron recognition and the evolution of the splicing machinery.
External linksMol Cell / PubMed:39809272
MethodsEM (single particle)
Resolution3.0 - 3.5 Å
Structure data

18984

8r7n

EMDB-18984, PDB-8r7n:
Overall structure of the U11 snRNP
Method: EM (single particle) / Resolution: 3.4 Å

51223

9gbw

EMDB-51223, PDB-9gbw:
Overall structure of the substrate-bound U11 snRNP
Method: EM (single particle) / Resolution: 3.5 Å

51225

9gbz

EMDB-51225, PDB-9gbz:
5'-lobe of the substrate-bound U11 snRNP
Method: EM (single particle) / Resolution: 3.4 Å

51226

9gc0

EMDB-51226, PDB-9gc0:
3'-lobe of the substrate-bound U11 snRNP
Method: EM (single particle) / Resolution: 3.2 Å

51233

9gcl

EMDB-51233, PDB-9gcl:
Structure of the U11 snRNP C-lobe
Method: EM (single particle) / Resolution: 3.0 Å

51234

9gcm

EMDB-51234, PDB-9gcm:
Structure of the U11 snRNP core
Method: EM (single particle) / Resolution: 3.1 Å

Source
  • homo sapiens (human)
KeywordsSPLICING / minor spliceosome / U11 snRNP / RNA-protein complex

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