The human cap-binding complex is functionally connected to the nuclear RNA exosome

Nat Struct Mol Biol. 2013 Dec;20(12):1367-76. doi: 10.1038/nsmb.2703. Epub 2013 Nov 24.

Abstract

Nuclear processing and quality control of eukaryotic RNA is mediated by the RNA exosome, which is regulated by accessory factors. However, the mechanism of exosome recruitment to its ribonucleoprotein (RNP) targets remains poorly understood. Here we report a physical link between the human exosome and the cap-binding complex (CBC). The CBC associates with the ARS2 protein to form CBC-ARS2 (CBCA) and then further connects, together with the ZC3H18 protein, to the nuclear exosome targeting (NEXT) complex, thus forming CBC-NEXT (CBCN). RNA immunoprecipitation using CBCN factors as well as the analysis of combinatorial depletion of CBCN and exosome components underscore the functional relevance of CBC-exosome bridging at the level of target RNA. Specifically, CBCA suppresses read-through products of several RNA families by promoting their transcriptional termination. We suggest that the RNP 5' cap links transcription termination to exosomal RNA degradation through CBCN.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exosome Multienzyme Ribonuclease Complex / chemistry
  • Exosome Multienzyme Ribonuclease Complex / metabolism
  • Exosome Multienzyme Ribonuclease Complex / physiology*
  • Humans
  • Immunoprecipitation
  • Nuclear Cap-Binding Protein Complex / chemistry
  • Nuclear Cap-Binding Protein Complex / metabolism
  • Nuclear Cap-Binding Protein Complex / physiology*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology
  • RNA Stability
  • Transcription Termination, Genetic

Substances

  • Nuclear Cap-Binding Protein Complex
  • Nuclear Proteins
  • SRRT protein, human
  • Exosome Multienzyme Ribonuclease Complex

Associated data

  • GEO/GSE52132
  • SRA/SRP031620