AKAP95 regulates splicing through scaffolding RNAs and RNA processing factors

Jing Hu, Alireza Khodadadi-Jamayran, Miaowei Mao, Kushani Shah, Zhenhua Yang, Md Talat Nasim, Zefeng Wang and Hao Jiang ()
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Jing Hu: UAB Stem Cell Institute, University of Alabama at Birmingham School of Medicine
Alireza Khodadadi-Jamayran: UAB Stem Cell Institute, University of Alabama at Birmingham School of Medicine
Miaowei Mao: Lineberger Comprehensive Cancer Center, University of North Carolina
Kushani Shah: UAB Stem Cell Institute, University of Alabama at Birmingham School of Medicine
Zhenhua Yang: UAB Stem Cell Institute, University of Alabama at Birmingham School of Medicine
Md Talat Nasim: University of Bradford School of Pharmacy
Zefeng Wang: Lineberger Comprehensive Cancer Center, University of North Carolina
Hao Jiang: UAB Stem Cell Institute, University of Alabama at Birmingham School of Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: Abstract 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, has a remarkable activity in enhancing chromatin transcription. In this study, we show that AKAP95 interacts with many factors involved in transcription and RNA processing, including selective groups of hnRNP proteins, through its N-terminal region, and directly regulates pre-mRNA splicing. AKAP95 binds preferentially to proximal intronic regions on pre-mRNAs in human transcriptome, and this binding requires its zinc-finger domains. By selectively coordinating with hnRNP H/F and U proteins, AKAP95 appears to mainly promote the inclusion of many exons in the genome. AKAP95 also directly interacts with itself. Taken together, our results establish AKAP95 as a mostly positive regulator of pre-mRNA splicing and a possible integrator of transcription and splicing regulation.

Date: 2016
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DOI: 10.1038/ncomms13347

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