Molecular composition of IMP1 ribonucleoprotein granules

Mol Cell Proteomics. 2007 May;6(5):798-811. doi: 10.1074/mcp.M600346-MCP200. Epub 2007 Feb 7.

Abstract

Localized mRNAs are transported to sites of local protein synthesis in large ribonucleoprotein (RNP) granules, but their molecular composition is incompletely understood. Insulin-like growth factor II mRNA-binding protein (IMP) zip code-binding proteins participate in mRNA localization, and in motile cells IMP-containing granules are dispersed around the nucleus and in cellular protrusions. We isolated the IMP1-containing RNP granules and found that they represent a unique RNP entity distinct from neuronal hStaufen and/or fragile X mental retardation protein granules, processing bodies, and stress granules. Granules were 100-300 nm in diameter and consisted of IMPs, 40 S ribosomal subunits, shuttling heterologous nuclear RNPs, poly(A)-binding proteins, and mRNAs. Moreover granules contained CBP80 and factors belonging to the exon junction complex and lacked eIF4E, eIF4G, and 60 S ribosomal subunits, indicating that embodied mRNAs are not translated. Granules embodied mRNAs corresponding to about 3% of the human embryonic kidney 293 mRNA transcriptome. Messenger RNAs encoding proteins participating in the secretory pathway and endoplasmic reticulum-associated quality control, as well as ubiquitin-dependent metabolism, were enriched in the granules, reinforcing the concept of RNP granules as post-transcriptional operons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cytoskeletal Proteins / metabolism
  • Fragile X Mental Retardation Protein / metabolism
  • Humans
  • Metabolic Networks and Pathways
  • Microscopy, Atomic Force
  • Proteomics
  • RNA, Messenger / analysis
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / metabolism
  • Ribonucleoproteins / chemistry*
  • Ribonucleoproteins / metabolism
  • Ribonucleoproteins / ultrastructure

Substances

  • Cytoskeletal Proteins
  • FMR1 protein, human
  • IGF2BP1 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • STAU1 protein, human
  • Fragile X Mental Retardation Protein