Heterogeneous nuclear ribonucleoprotein C modulates translation of c-myc mRNA in a cell cycle phase-dependent manner

Mol Cell Biol. 2003 Jan;23(2):708-20. doi: 10.1128/MCB.23.2.708-720.2003.

Abstract

The c-myc proto-oncogene plays a key role in the proliferation, differentiation, apoptosis, and regulation of the cell cycle. Recently, it was demonstrated that the 5' nontranslated region (5' NTR) of human c-myc mRNA contains an internal ribosomal entry site (IRES). In this study, we investigated cellular proteins interacting with the IRES element of c-myc mRNA. Heterogeneous nuclear ribonucleoprotein C (hnRNP C) was identified as a cellular protein that interacts specifically with a heptameric U sequence in the c-myc IRES located between two alternative translation initiation codons CUG and AUG. Moreover, the addition of hnRNP C1 in an in vitro translation system enhanced translation of c-myc mRNA. Interestingly, hnRNP C was partially relocalized from the nucleus, where most of the hnRNP C resides at interphase, to the cytoplasm at the G(2)/M phase of the cell cycle. Coincidently, translation mediated through the c-myc IRES was increased at the G(2)/M phase when cap-dependent translation was partially inhibited. On the other hand, a mutant c-myc mRNA lacking the hnRNP C-binding site, showed a decreased level of translation at the G(2)/M phase compared to that of the wild-type message. Taken together, these findings suggest that hnRNP C, via IRES binding, modulates translation of c-myc mRNA in a cell cycle phase-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Apoptosis
  • Binding Sites
  • Biotinylation
  • Blotting, Northern
  • Cell Cycle
  • Cell Differentiation
  • Cell Division
  • Cell Separation
  • Codon, Initiator
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • G2 Phase
  • Genes, Reporter
  • Glutathione Transferase / metabolism
  • HeLa Cells
  • Heterogeneous-Nuclear Ribonucleoprotein Group C / chemistry*
  • Heterogeneous-Nuclear Ribonucleoprotein Group C / metabolism
  • Humans
  • Immunoblotting
  • Mitosis
  • Models, Genetic
  • Mutation
  • Plasmids / metabolism
  • Protein Binding
  • Protein Biosynthesis*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Ribosomes / metabolism
  • Transcription, Genetic
  • Ultraviolet Rays

Substances

  • 5' Untranslated Regions
  • Codon, Initiator
  • Heterogeneous-Nuclear Ribonucleoprotein Group C
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Glutathione Transferase