title: Selective nuclear export of specific classes of mRNA from mammalian nuclei is promoted by GANP.
abstract: The nuclear phase of the gene expression pathway culminates in the export of mature messenger RNAs (mRNAs) to the cytoplasm through nuclear pore complexes. GANP (germinal- centre associated nuclear protein) promotes the transfer of mRNAs bound to the transport factor NXF1 to nuclear pore complexes. Here, we demonstrate that GANP, subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex, promotes selective nuclear export of a specific subset of mRNAs whose transport depends on NXF1. Genome-wide gene expression profiling showed that half of the transcripts whose nuclear export was impaired following NXF1 depletion also showed reduced export when GANP was depleted. GANP-dependent transcripts were highly expressed, yet short-lived, and were highly enriched in those encoding central components of the gene expression machinery such as RNA synthesis and processing factors. After injection into Xenopus oocyte nuclei, representative GANP-dependent transcripts showed faster nuclear export kinetics than representative transcripts that were not influenced by GANP depletion. We propose that GANP promotes the nuclear export of specific classes of mRNAs that may facilitate rapid changes in gene expression.
authors: MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Box 197, Biomedical Campus, Cambridge CB2 0XZ, UK, The Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK, Wellcome Trust, Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK and Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
authors: Vihandha O
authors: VO
authors: Wickramasinghe
authors: Robert
authors: R
authors: Andrews
authors: Peter
authors: P
authors: Ellis
authors: Cordelia
authors: C
authors: Langford
authors: John B
authors: JB
authors: Gurdon
authors: Murray
authors: M
authors: Stewart
authors: Ashok R
authors: AR
authors: Venkitaraman
authors: Ronald A
authors: RA
authors: Laskey
mesh_terms: D000123:Acetyltransferases / Q000502:physiology*; D021581:Active Transport, Cell Nucleus; D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D029543:Nucleocytoplasmic Transport Proteins / Q000502:physiology; D012333:RNA, Messenger / Q000145:classification / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000502:physiology; D014981:Xenopus
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C122111:NXF1 protein, human; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000123:Acetyltransferases; C406825:MCM3AP protein, human