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.