Yes / Alternative 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. / This work was supported by a UAB start-up fund to H.J.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/10168 |
| Date | 08 November 2016 |
| Creators | Hu, J., Khodadadi-Jamayran, A., Mao, M., Shah, K., Yang, Z., Nasim, Md. Talat, Wang, Z., Jiang, H. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Published version paper |
| Rights | © 2016 Hu J et al. This work is licensed under a CC BY license (Creative Commons Attribution 4.0 International License) |
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