AKAP95 regulates splicing through scaffolding RNAs and RNA processing factors.
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.
Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35294, USA.
Jing
J
Hu
Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35294, USA.
Alireza
A
Khodadadi-Jamayran
Lineberger Comprehensive Cancer Center, Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Miaowei
M
Mao
Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35294, USA.
Kushani
K
Shah
Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35294, USA.
Zhenhua
Z
Yang
University of Bradford School of Pharmacy, Bradford BD7 1DP, UK.
Md Talat
MT
Nasim
Lineberger Comprehensive Cancer Center, Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Zefeng
Z
Wang
Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35294, USA.
Hao
H
Jiang
D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D005091:Exons / Q000235:genetics; D006367:HeLa Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007438:Introns / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism*; D014158:Transcription, Genetic
D054758:A Kinase Anchor Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012322:RNA Precursors; D012334:RNA, Neoplasm; C485099:AKAP8 protein, human; C412048:HYCC1 protein, human