Article abstract
Nature Structural & Molecular Biology 15, 183 - 191 (2008)
Published online: 13 January 2008 | doi:10.1038/nsmb.1375
Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome
Shalini Sharma1, Lori A Kohlstaedt2, Andrey Damianov1, Donald C Rio3 & Douglas L Black1,4
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.
- Howard Hughes Medical Institute, University of California, Los Angeles, MRL5-748, Charles E. Young Drive South, Los Angeles, California 90095, USA.
- Cancer Research Laboratory, Mass Spectrometry Facility, University of California, Berkeley, 525 Life Science Addition.
- Department of Molecular and Cell Biology, University of California, Berkeley, 16 Barker Hall, Berkeley, California, 94720 USA.
- Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, 1602 Molecular Sciences Building, 405 Hilgard Avenue, Los Angeles, California 90095, USA.
Correspondence to: Douglas L Black1,4 e-mail: dougb@microbio.ucla.edu
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