Cell Reports
Volume 10, Issue 2, 13 January 2015, Pages 178-192
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Article
The Human Nuclear Exosome Targeting Complex Is Loaded onto Newly Synthesized RNA to Direct Early Ribonucleolysis

https://doi.org/10.1016/j.celrep.2014.12.026Get rights and content
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open access

Highlights

  • RBM7 is loaded promiscuously onto newly synthesized RNA

  • RBM7/NEXT defines an early nuclear RNA decay pathway

  • RBM7/NEXT triggers exosome activity at snoRNA-encoding introns

  • RBM7/NEXT assigns many lncRNAs for nuclear degradation

Summary

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.

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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Co-first author

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Present address: Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark

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Present address: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria

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Present address: Division of Genomic Technologies, RIKEN, Yokohama 230-0045, Japan