title: The Exon Junction Complex Controls the Efficient and Faithful Splicing of a Subset of Transcripts Involved in Mitotic Cell-Cycle Progression.
abstract: The exon junction complex (EJC) that is deposited onto spliced mRNAs upstream of exon-exon junctions plays important roles in multiple post-splicing gene expression events, such as mRNA export, surveillance, localization, and translation. However, a direct role for the human EJC in pre-mRNA splicing has not been fully understood. Using HeLa cells, we depleted one of the EJC core components, Y14, and the resulting transcriptome was analyzed by deep sequencing (RNA-Seq) and confirmed by RT-PCR. We found that Y14 is required for efficient and faithful splicing of a group of transcripts that is enriched in short intron-containing genes involved in mitotic cell-cycle progression. Tethering of EJC core components (Y14, eIF4AIII or MAGOH) to a model reporter pre-mRNA harboring a short intron showed that these core components are prerequisites for the splicing activation. Taken together, we conclude that the EJC core assembled on pre-mRNA is critical for efficient and faithful splicing of a specific subset of short introns in mitotic cell cycle-related genes.
authors.affiliation: Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodaicho, Nadaku, Kobe 657-8501, Japan. fukumura@fujita-hu.ac.jp.|Division of Gene Expression Mechanism, Institute for Comprehensive Medical Science (ICMS), Fujita Health University, Toyoake, Aichi 470-1192, Japan. fukumura@fujita-hu.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Fukumura
authors.affiliation: Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. s-wakaba@hgc.jp.|Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan. s-wakaba@hgc.jp.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Wakabayashi
authors.affiliation: Laboratory for Malignancy Control Research, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan. kataoka.naoyuki.6m@kyoto-u.ac.jp.|Laboratory of Cell Regulation, Departments of Applied Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. kataoka.naoyuki.6m@kyoto-u.ac.jp.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kataoka
authors.affiliation: Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodaicho, Nadaku, Kobe 657-8501, Japan. hsaka@kobe-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakamoto
authors.affiliation: Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan. ysuzuki@k.u-tokyo.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. knakai@ims.u-tokyo.ac.jp.|Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan. knakai@ims.u-tokyo.ac.jp.
authors.forename: Kenta
authors.initials: K
authors.lastname: Nakai
authors.affiliation: Division of Gene Expression Mechanism, Institute for Comprehensive Medical Science (ICMS), Fujita Health University, Toyoake, Aichi 470-1192, Japan. mayeda@fujita-hu.ac.jp.
authors.forename: Akila
authors.initials: A
authors.lastname: Mayeda
authors.affiliation: Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodaicho, Nadaku, Kobe 657-8501, Japan. kunio@kobe-u.ac.jp.
authors.forename: Kunio
authors.initials: K
authors.lastname: Inoue
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D008938:Mitosis / Q000235:genetics*; D008957:Models, Genetic; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D012322:RNA Precursors; D012333:RNA, Messenger
keywords: Y14; exon junction complex (EJC); mitotic cell-cycle; pre-mRNA splicing