title: The integrator complex is required for integrity of Cajal bodies.
abstract: The nucleus in eukaryotic cells is a highly organized and dynamic structure containing numerous subnuclear bodies. The morphological appearance of nuclear bodies seems to be a reflection of ongoing functions, such as DNA replication, transcription, repair, RNA processing and RNA transport. The integrator complex mediates processing of small nuclear RNA (snRNA), so it might play a role in nuclear body formation. Here, we show that the integrator complex is essential for integrity of the Cajal body. Depletion of INTS4, an integrator complex subunit, abrogated 3'-end processing of snRNA. A defect in this activity caused a significant accumulation of the Cajal body marker protein coilin in nucleoli. Some fractions of coilin still formed nucleoplasmic foci; however, they were free of other Cajal body components, such as survival of motor neuron protein (SMN), Sm proteins and snRNAs. SMN and Sm proteins formed striking cytoplasmic granules. These findings demonstrate that the integrator complex is essential for snRNA maturation and Cajal body homeostasis.
authors.affiliation: Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima, Japan. htakata@lab.nig.ac.jp
authors.forename: Hideaki
authors.initials: H
authors.lastname: Takata
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishijima
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Maeshima
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Shibahara
mesh_terms: D021581:Active Transport, Cell Nucleus; D002466:Cell Nucleolus / Q000378:metabolism; D020541:Coiled Bodies / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D021381:Protein Transport; D012342:RNA, Small Nuclear / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D055532:SMN Complex Proteins / Q000378:metabolism
chemical_list: C581361:INTS4 protein, human; D009687:Nuclear Proteins; D012342:RNA, Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins; C068921:p80-coilin; D012260:Ribonucleases