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dc.contributor.authorKeppetipola, Niroshika M
dc.contributor.authorYeom, Kyu-Hyeon
dc.contributor.authorHernandez, Adrian L
dc.contributor.authorBui, Tessa
dc.contributor.authorSharma, Shalini
dc.contributor.authorBlack, Douglas L
dc.date.accessioned2019-10-31T00:45:18Z
dc.date.available2019-10-31T00:45:18Z
dc.date.issued2016-06-10
dc.identifier.citationKeppetipola, N. M., Yeom, K. H., Hernandez, A. L., Bui, T., Sharma, S., & Black, D. L. (2016). Multiple determinants of splicing repression activity in the polypyrimidine tract binding proteins, PTBP1 and PTBP2. Rna, 22(8), 1172-1180.en_US
dc.identifier.issn1355-8382
dc.identifier.pmid27288314
dc.identifier.doi10.1261/rna.057505.116
dc.identifier.urihttp://hdl.handle.net/10150/634935
dc.description.abstractMost human genes generate multiple protein isoforms through alternative pre-mRNA splicing, but the mechanisms controlling alternative splicing choices by RNA binding proteins are not well understood. These proteins can have multiple paralogs expressed in different cell types and exhibiting different splicing activities on target exons. We examined the paralogous polypyrimidine tract binding proteins PTBP1 and PTBP2 to understand how PTBP1 can exhibit greater splicing repression activity on certain exons. Using both an in vivo coexpression assay and an in vitro splicing assay, we show that PTBP1 is more repressive than PTBP2 per unit protein on a target exon. Constructing chimeras of PTBP1 and 2 to determine amino acid features that contribute to their differential activity, we find that multiple segments of PTBP1 increase the repressive activity of PTBP2. Notably, when either RRM1 of PTBP2 or the linker peptide separating RRM2 and RRM3 are replaced with the equivalent PTBP1 sequences, the resulting chimeras are highly active for splicing repression. These segments are distinct from the known region of interaction for the PTBP1 cofactors Raver1 and Matrin3 in RRM2. We find that RRM2 of PTBP1 also increases the repression activity of an otherwise PTBP2 sequence, and that this is potentially explained by stronger binding by Raver1. These results indicate that multiple features over the length of the two proteins affect their ability to repress an exon.en_US
dc.description.sponsorshipNational Institutes of Health Ruth L. Kirschstein National Research Service Award (NIH-NRSA) [1F32GM093533]; CSUPERB New Investigator Award; NIH [R01GM049662, R21CA170786]; UCLA Broad Stem Cell Research Center's Training Programen_US
dc.language.isoenen_US
dc.publisherCOLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPTen_US
dc.rightsCopyright © 2016 Keppetipola et al. This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http:// rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.en_US
dc.subjectRNA binding proteinsen_US
dc.subjectalternative splicingen_US
dc.titleMultiple determinants of splicing repression activity in the polypyrimidine tract binding proteins, PTBP1 and PTBP2en_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Dept Basic Med Sci, Coll Meden_US
dc.identifier.journalRNAen_US
dc.description.note12 month embargo; published online: 10 June 2016en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleRNA (New York, N.Y.)
refterms.dateFOA2017-06-10T00:00:00Z


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