title: Son maintains accurate splicing for a subset of human pre-mRNAs.
abstract: Serine-arginine-rich (SR) proteins play a key role in alternative pre-mRNA splicing in eukaryotes. We recently showed that a large SR protein called Son has unique repeat motifs that are essential for maintaining the subnuclear organization of pre-mRNA processing factors in nuclear speckles. Motif analysis of Son highlights putative RNA interaction domains that suggest a direct role for Son in pre-mRNA splicing. Here, we used in situ approaches to show that Son localizes to a reporter minigene transcription site, and that RNAi-mediated Son depletion causes exon skipping on reporter transcripts at this transcription site. A genome-wide exon microarray analysis was performed to identify human transcription and splicing targets of Son. Our data show that Son-regulated splicing encompasses all known types of alternative splicing, the most common being alternative splicing of cassette exons. We confirmed that knockdown of Son leads to exon skipping in pre-mRNAs for chromatin-modifying enzymes, including ADA, HDAC6 and SetD8. This study reports a comprehensive view of human transcription and splicing targets for Son in fundamental cellular pathways such as integrin-mediated cell adhesion, cell cycle regulation, cholesterol biosynthesis, apoptosis and epigenetic regulation of gene expression.
authors.affiliation: Biomedical Sciences Ph.D. Program, Wright State University, Dayton, OH 45435,  USA.
authors.forename: Alok
authors.initials: A
authors.lastname: Sharma
authors.forename: Michael
authors.initials: M
authors.lastname: Markey
authors.forename: Keshia
authors.initials: K
authors.lastname: Torres-Muñoz
authors.forename: Sapna
authors.initials: S
authors.lastname: Varia
authors.forename: Madhavi
authors.initials: M
authors.lastname: Kadakia
authors.forename: Athanasios
authors.initials: A
authors.lastname: Bubulya
authors.forename: Paula A
authors.initials: PA
authors.lastname: Bubulya
mesh_terms: D017398:Alternative Splicing; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D034622:RNA Interference; D012322:RNA Precursors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D000068103:Serine-Arginine Splicing Factors; D008941:Spindle Apparatus / Q000648:ultrastructure; D014158:Transcription, Genetic; D014335:Tropomyosin / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C088203:SON protein, human; D014335:Tropomyosin; D000068103:Serine-Arginine Splicing Factors