The human nuclear exosome targeting complex is loaded onto newly synthesized RNA to direct early ribonucleolysis

Cell Rep. 2015 Jan 13;10(2):178-92. doi: 10.1016/j.celrep.2014.12.026. Epub 2015 Jan 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Exosome Multienzyme Ribonuclease Complex / metabolism*
  • Exosomes / metabolism
  • HeLa Cells
  • Humans
  • Protein Binding
  • RNA / chemistry
  • RNA / metabolism*
  • RNA Polymerase III / metabolism
  • RNA Precursors / chemistry
  • RNA Precursors / metabolism
  • RNA, Long Noncoding / chemistry
  • RNA, Long Noncoding / metabolism
  • RNA, Small Nuclear / chemistry
  • RNA, Small Nuclear / metabolism
  • RNA, Small Nucleolar / chemistry
  • RNA, Small Nucleolar / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism


  • RBM7 protein, human
  • RNA Precursors
  • RNA, Long Noncoding
  • RNA, Small Nuclear
  • RNA, Small Nucleolar
  • RNA-Binding Proteins
  • RNA
  • RNA Polymerase III
  • Exosome Multienzyme Ribonuclease Complex

Associated data

  • GEO/GSE48286
  • GEO/GSE52132
  • GEO/GSE63496
  • GEO/GSE63791