Structure of the RBM7-ZCCHC8 core of the NEXT complex reveals connections to splicing factors

Nat Commun. 2016 Dec 1:7:13573. doi: 10.1038/ncomms13573.

Abstract

The eukaryotic RNA exosome participates extensively in RNA processing and degradation. In human cells, three accessory factors (RBM7, ZCCHC8 and hMTR4) interact to form the nuclear exosome targeting (NEXT) complex, which directs a subset of non-coding RNAs for exosomal degradation. Here we elucidate how RBM7 is incorporated in the NEXT complex. We identify a proline-rich segment of ZCCHC8 as the interaction site for the RNA-recognition motif (RRM) of RBM7 and present the crystal structure of the corresponding complex at 2.0 Å resolution. On the basis of the structure, we identify a proline-rich segment within the splicing factor SAP145 with strong similarity to ZCCHC8. We show that this segment of SAP145 not only binds the RRM region of another splicing factor SAP49 but also the RRM of RBM7. These dual interactions of RBM7 with the exosome and the spliceosome suggest a model whereby NEXT might recruit the exosome to degrade intronic RNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Conserved Sequence
  • Crystallography, X-Ray
  • DNA Mutational Analysis
  • Evolution, Molecular
  • HeLa Cells
  • Humans
  • Multiprotein Complexes / metabolism*
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism*
  • Proline / metabolism
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Secondary
  • Protein Subunits / metabolism
  • RNA Splicing
  • RNA Splicing Factors / metabolism*
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / metabolism*
  • Structure-Activity Relationship

Substances

  • Carrier Proteins
  • Multiprotein Complexes
  • Nuclear Proteins
  • Protein Subunits
  • RBM7 protein, human
  • RNA Splicing Factors
  • RNA-Binding Proteins
  • SF3B2 protein, human
  • ZCCHC8 protein, human
  • Proline