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dc.contributor.authorHu, J.*
dc.contributor.authorKhodadadi-Jamayran, A.*
dc.contributor.authorMao, M.*
dc.contributor.authorShah, K.*
dc.contributor.authorYang, Z.*
dc.contributor.authorNasim, Md. Talat*
dc.contributor.authorWang, Z.*
dc.contributor.authorJiang, H.*
dc.date.accessioned2016-10-31T15:48:49Z
dc.date.available2016-10-31T15:48:49Z
dc.date.issued2016-11
dc.identifier.citationHu J, Khodadadi-Jamayran A, Mao M et al (2016) AKAP95 regulates splicing through scaffolding RNAs and RNA processing factors. Nature Communications. 7: Article 13347.en_US
dc.identifier.urihttp://hdl.handle.net/10454/10168
dc.descriptionYesen_US
dc.description.abstractAlternative splicing of pre-mRNAs significantly contributes to the complexity of gene expression in higher organisms, but the regulation of the splice site selection remains incompletely understood. We have previously demonstrated that a chromatin-associated protein, AKAP95 (AKAP8), has a remarkable activity in enhancing chromatin transcription. In this study, we have shown that AKAP95 physically interacts with many factors involved in transcription and RNA processing, and functionally regulates pre-mRNA splicing. AKAP95 directly promotes splicing in vitro and the inclusion of a specific exon of an endogenous gene FAM126A. The N-terminal YG-rich domain of AKAP95 is important for its binding to RNA processing factors including selective groups of hnRNP proteins, and its zinc finger domains are critical for pre-mRNA binding. Genome-wide binding assays revealed that AKAP95 bound preferentially to proximal intronic regions on a large number of pre-mRNAs in human transcriptome, and AKAP95 depletion predominantly resulted in reduced inclusion of many exons. AKAP95 also selectively coordinates with hnRNP H/F and U proteins in regulating alternative splicing events. We have further shown that AKAP95 directly interacts with itself. Taken together, our results establish AKAP95 as a novel and mostly positive regulator of premRNA splicing and a possible integrator of transcription and splicing regulation, and support a model that AKAP95 facilitates the splice site communication by looping out introns through both RNA-binding and protein-protein interaction.en_US
dc.description.sponsorshipThis work was supported by a UAB start-up fund to H.J.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1038/ncomms13347en_US
dc.rights© 2016 Hu J et al. This work is licensed under a CC BY license (Creative Commons Attribution 4.0 International License)en_US
dc.subjectAKAP95; Splicing; RNA processing;en_US
dc.titleAKAP95 regulates splicing through scaffolding RNAs and RNA processing factorsen_US
dc.status.refereedYesen_US
dc.date.Accepted2016-09-22
dc.date.application2016-11-08
dc.typeArticleen_US
dc.type.versionPublished version paperen_US
refterms.dateFOA2018-07-25T15:36:13Z


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