Abstract:
:The polypyrimidine tract binding protein (PTB) binds pre-mRNAs to alter splice-site choice. We characterized a series of spliceosomal complexes that assemble on a pre-mRNA under conditions of either PTB-mediated splicing repression or its absence. In the absence of repression, exon definition complexes that were assembled downstream of the regulated exon could progress to pre-spliceosomal A complexes and functional spliceosomes. Under PTB-mediated repression, assembly was arrested at an A-like complex that was unable to transition to spliceosomal complexes. Trans-splicing experiments indicated that, even when the U1 and U2 small nuclear ribonucleoprotein particles (snRNPs) are properly bound to the upstream and downstream exons, the presence of PTB prevents the interaction of the two exon complexes. Proteomic analyses of these complexes provide a new description of exon definition complexes, and indicate that splicing regulators can act on the transition between the exon definition complex and an intron-defined spliceosome.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Sharma S,Kohlstaedt LA,Damianov A,Rio DC,Black DLdoi
10.1038/nsmb.1375subject
Has Abstractpub_date
2008-02-01 00:00:00pages
183-91issue
2eissn
1545-9993issn
1545-9985pii
nsmb.1375journal_volume
15pub_type
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