Large-scale remodeling of a repressed exon ribonucleoprotein to an exon definition complex active for splicing
AuthorWongpalee, Somsakul Pop
Wohlschlegel, James A
Black, Douglas L
AffiliationUniv Arizona, Dept Basic Med Sci
MetadataShow full item record
PublisherELIFE SCIENCES PUBLICATIONS LTD
CitationLarge-scale remodeling of a repressed exon ribonucleoprotein to an exon definition complex active for splicing 2016, 5 eLife
Rights© Copyright Wongpalee et al. This article is distributed under the terms of the Creative Commons Attribution License.
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AbstractPolypyrimidine-tract binding protein PTBP1 can repress splicing during the exon definition phase of spliceosome assembly, but the assembly steps leading to an exon definition complex (EDC) and how PTBP1 might modulate them are not clear. We found that PTBP1 binding in the flanking introns allowed normal U2AF and U1 snRNP binding to the target exon splice sites but blocked U2 snRNP assembly in HeLa nuclear extract. Characterizing a purified PTBP1-repressed complex, as well as an active early complex and the final EDC by SILAC-MS, we identified extensive PTBP1-modulated changes in exon RNP composition. The active early complex formed in the absence of PTBP1 proceeded to assemble an EDC with the eviction of hnRNP proteins, the late recruitment of SR proteins, and binding of the U2 snRNP. These results demonstrate that during early stages of splicing, exon RNP complexes are highly dynamic with many proteins failing to bind during PTBP1 arrest.
NotePaid Open Access after January 2017*
VersionFinal published version
SponsorsNational Institute of General Medical Sciences [R01GM049662, R01GM089778]; Howard Hughes Medical Institute; National Cancer Institute [R21CA170786]; Institute for the Promotion of Teaching Science and Technology, Thailand Royal Thai Fellowship
Except where otherwise noted, this item's license is described as © Copyright Wongpalee et al. This article is distributed under the terms of the Creative Commons Attribution License.