title: The human nuclear exosome targeting complex is loaded onto newly synthesized RNA to direct early ribonucleolysis.
abstract: The RNA exosome complex constitutes the major nuclear eukaryotic 3'-5' exonuclease. Outside of nucleoli, the human nucleoplasmic exosome is directed to some of its substrates by the nuclear exosome targeting (NEXT) complex. How NEXT targets RNA has remained elusive. Using an in vivo crosslinking approach, we report global RNA binding sites of RBM7, a key component of NEXT. RBM7 associates broadly with RNA polymerase II-derived RNA, including pre-mRNA and short-lived exosome substrates such as promoter upstream transcripts (PROMPTs), enhancer RNAs (eRNAs), and 3'-extended products from snRNA and replication-dependent histone genes. Within pre-mRNA, RBM7 accumulates at the 3' ends of introns, and pulse-labeling experiments demonstrate that RBM7/NEXT defines an early exosome-targeting pathway for 3'-extended snoRNAs derived from such introns. We propose that RBM7 is generally loaded onto newly synthesized RNA to accommodate exosome action in case of available unprotected RNA 3' ends.
authors.affiliation: Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland; Department of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, 02-106 Warsaw, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Lubas
authors.affiliation: Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark.
authors.forename: Peter Refsing
authors.initials: PR
authors.lastname: Andersen
authors.affiliation: Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark.
authors.forename: Aleks
authors.initials: A
authors.lastname: Schein
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland; Department of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, 02-106 Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Dziembowski
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kudla
authors.affiliation: Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark. Electronic address: thj@mb.au.dk.
authors.forename: Torben Heick
authors.initials: TH
authors.lastname: Jensen
mesh_terms: D001665:Binding Sites; D063326:Exosome Multienzyme Ribonuclease Complex / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D012320:RNA Polymerase III / Q000378:metabolism; D012322:RNA Precursors / Q000737:chemistry / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000737:chemistry / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000737:chemistry / Q000378:metabolism; D020537:RNA, Small Nucleolar / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: C000596172:RBM7 protein, human; D012322:RNA Precursors; D062085:RNA, Long Noncoding; D012342:RNA, Small Nuclear; D020537:RNA, Small Nucleolar; D016601:RNA-Binding Proteins; D012313:RNA; D012320:RNA Polymerase III; D063326:Exosome Multienzyme Ribonuclease Complex