title: Global splicing pattern reversion during somatic cell reprogramming.
abstract: Alternative splicing generates multiple transcripts from a single gene, and cell-type-specific splicing profiles are important for the properties and functions of the cells. Recently, somatic cells have been shown to undergo dedifferentiation after the forced expression of transcription factors. However, it remains unclear whether somatic cell splicing is reorganized during reprogramming. Here, by combining deep sequencing with high-throughput absolute qRT-PCR, we show that somatic splicing profiles revert to pluripotent ones during reprogramming. Remarkably, the splicing pattern in pluripotent stem cells resembles that in testes, and the regulatory regions have specific characteristics in length and sequence. Furthermore, our siRNA screen has identified RNA-binding proteins that regulate splicing events in iPSCs. We have then demonstrated that two of the RNA-binding proteins, U2af1 and Srsf3, play a role in somatic cell reprogramming. Our results indicate that the drastic alteration in splicing represents part of the molecular network involved in the reprogramming process.
authors.affiliation: Department of Reprogramming Science, Center for iPS Cell Research and Application, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Ohta
authors.forename: Eisuke
authors.initials: E
authors.lastname: Nishida
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamanaka
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D002460:Cell Line; D065150:Cellular Reprogramming; D005091:Exons; D005786:Gene Expression Regulation; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D000072668:Splicing Factor U2AF
chemical_list: D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C106161:Srsf3 protein, mouse; C000607495:Zrsr1 protein, mouse; D000068103:Serine-Arginine Splicing Factors