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The Human Nuclear Exosome Targeting Complex Is Loaded onto Newly Synthesized RNA to Direct Early Ribonucleolysis

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  • Michal Szymon Lubas, Denmark
  • Peter Refsing Andersen
  • Aleks Schein, Denmark
  • Andrzej Dziembowski, Department of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Poland
  • Grzegorz Kudla, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom
  • Torben Heick Jensen

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.

Original languageEnglish
JournalCell Reports
Pages (from-to)178-183
Number of pages6
Publication statusPublished - 13 Jan 2015

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