7w5a
From Proteopedia
The cryo-EM structure of human pre-C*-II complex
Structural highlights
FunctionRBM22_HUMAN Involved in the first step of pre-mRNA splicing. Binds directly to the internal stem-loop (ISL) domain of the U6 snRNA and to the pre-mRNA intron near the 5' splice site during the activation and catalytic phases of the spliceosome cycle. Involved in both translocations of the nuclear SLU7 to the cytoplasm and the cytosolic calcium-binding protein PDCD6 to the nucleus upon cellular stress responses.[1] [2] [3] Publication Abstract from PubMedPre-mRNA splicing involves two sequential reactions: branching and exon ligation. The C complex after branching undergoes remodeling to become the C( *) complex, which executes exon ligation. Here, we report cryo-EM structures of two intermediate human spliceosomal complexes, pre-C( *)-I and pre-C( *)-II, both at 3.6 A. In both structures, the 3' splice site is already docked into the active site, the ensuing 3' exon sequences are anchored on PRP8, and the step II factor FAM192A contacts the duplex between U2 snRNA and the branch site. In the transition of pre-C( *)-I to pre-C( *)-II, the step II factors Cactin, FAM32A, PRKRIP1, and SLU7 are recruited. Notably, the RNA helicase PRP22 is positioned quite differently in the pre-C( *)-I, pre-C( *)-II, and C( *) complexes, suggesting a role in 3' exon binding and proofreading. Together with information on human C and C( *) complexes, our studies recapitulate a molecular choreography of the C-to-C( *) transition, revealing mechanistic insights into exon ligation. Mechanism of exon ligation by human spliceosome.,Zhan X, Lu Y, Zhang X, Yan C, Shi Y Mol Cell. 2022 Aug 4;82(15):2769-2778.e4. doi: 10.1016/j.molcel.2022.05.021. Epub , 2022 Jun 14. PMID:35705093[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also
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Categories: Homo sapiens | Large Structures | Lu Y | Shi Y | Zhan X
