title: THOC5 controls 3'end-processing of immediate early genes via interaction with polyadenylation specific factor 100 (CPSF100).
abstract: Transcription of immediate early genes (IEGs) in response to extrinsic and intrinsic signals is tightly regulated at multiple stages. It is known that untranslated regions of the RNA can play a role in these processes. Here we show that THOC5, a member of the TREX (transcription/export) complex, plays a role in expression of only a subset of constitutively active genes, however transcriptome analysis reveals that more than 90% of IEG were not induced by serum in THOC5 depleted cells. Furthermore, THOC5 depletion does not influence the expression of the most rapidly induced IEGs, e.g. Fos and Jun. One group of THOC5 target genes, including Id1, Id3 and Wnt11 transcripts, were not released from chromatin in THOC5 depleted cells. Genes in another group, including Myc and Smad7 transcripts, were released with shortening of 3'UTR by alternative cleavage, and were spliced but export was impaired in THOC5 depleted cells. By interactome analysis using THOC5 as bait, we show that upon stimulation with serum THOC5 forms a complex with polyadenylation-specific factor 100 (CPSF100). THOC5 is required for recruitment of CPSF100 to 3'UTR of THOC5 target genes. These data suggest the presence of a novel mechanism for the control of IEG response by THOC5 via 3'end-processing.
authors.affiliation: Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, D-30623 Hannover, Germany.
authors.forename: Doan Duy Hai
authors.initials: DD
authors.lastname: Tran
authors.affiliation: Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, D-30623 Hannover, Germany.
authors.forename: Shashank
authors.initials: S
authors.lastname: Saran
authors.affiliation: Stem Cell and Leukaemia Proteomics Laboratory, The University of Manchester, Manchester Academic Health Science Centre, 27 Palatine Road, Withington Manchester, M20 3LJ UK.
authors.forename: Andrew J K
authors.initials: AJ
authors.lastname: Williamson
authors.affiliation: Stem Cell and Leukaemia Proteomics Laboratory, The University of Manchester, Manchester Academic Health Science Centre, 27 Palatine Road, Withington Manchester, M20 3LJ UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pierce
authors.affiliation: Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, D-30623 Hannover, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Dittrich-Breiholz
authors.affiliation: Pädiatrische Pneumologie OE6710 Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, D-30623 Hannover, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Wiehlmann
authors.affiliation: Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, D-30623 Hannover, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Koch
authors.affiliation: Stem Cell and Leukaemia Proteomics Laboratory, The University of Manchester, Manchester Academic Health Science Centre, 27 Palatine Road, Withington Manchester, M20 3LJ UK.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Whetton
authors.affiliation: Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, D-30623 Hannover, Germany tamura.teruko@Mh-hannover.de.
authors.forename: Teruko
authors.initials: T
authors.lastname: Tamura
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002460:Cell Line; D039223:Cleavage And Polyadenylation Specificity Factor / Q000378:metabolism*; D017781:Genes, Immediate-Early; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D026721:RNA 3' End Processing; D012326:RNA Splicing; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D039223:Cleavage And Polyadenylation Specificity Factor; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D051906:Smad7 Protein; C559981:THOC5 protein, mouse