Atomic modeling of the ITS2 ribosome assembly subcomplex from cryo-EM together with mass spectrometry-identified protein-protein crosslinks

Protein Sci. 2017 Jan;26(1):103-112. doi: 10.1002/pro.3045. Epub 2016 Oct 13.

Abstract

The assembly of ribosomal subunits starts in the nucleus, initiated by co-transcriptional folding of nascent ribosomal RNA (rRNA) transcripts and binding of ribosomal proteins and assembly factors. The internal transcribed spacer 2 (ITS2) is a precursor sequence to be processed from the intermediate 27S rRNA in the nucleoplasm; its removal is required for nuclear export of pre-60S particles. The proper processing of the ITS2 depends on multiple associated assembly factors and RNases. However, none of the structures of the known ITS2-binding factors is available. Here, we describe the modeling of the ITS2 subcomplex, including five assembly factors Cic1, Nop7, Nop15, Nop53, and Rlp7, using a combination of cryo-electron microscopy and cross-linking of proteins coupled with mass spectrometry approaches. The resulting atomic models provide structural insights into their function in ribosome assembly, and establish a framework for further dissection of their molecular roles in ITS2 processing.

Keywords: CXMS; Cic1; ITS2; Nop15; Nop53; Nop7; Rlp7; cross-linking; cryo-EM; ribosome assembly.

MeSH terms

  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Cryoelectron Microscopy
  • Mass Spectrometry
  • Models, Molecular*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • RNA, Ribosomal / chemistry
  • RNA, Ribosomal / metabolism
  • RNA, Ribosomal / ultrastructure*
  • Ribosomal Proteins / chemistry
  • Ribosomal Proteins / metabolism
  • Ribosome Subunits, Large, Eukaryotic / chemistry
  • Ribosome Subunits, Large, Eukaryotic / metabolism
  • Ribosome Subunits, Large, Eukaryotic / ultrastructure*
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / ultrastructure*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Carrier Proteins
  • Cic1 protein, S cerevisiae
  • NOP7 protein, S cerevisiae
  • Nop15 protein, S cerevisiae
  • Nop53 protein, S cerevisiae
  • Nuclear Proteins
  • RLP7 protein, S cerevisiae
  • RNA, Ribosomal
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins

Associated data

  • PDB/3u5e
  • PDB/3JCT