Eukaryotic Initiation Factor 4H Is under Transcriptional Control of p65/NF-κB

PLoS One. 2013 Jun 11;8(6):e66087. doi: 10.1371/journal.pone.0066087. Print 2013.

Abstract

Protein synthesis is mainly regulated at the initiation step, allowing the fast, reversible and spatial control of gene expression. Initiation of protein synthesis requires at least 13 translation initiation factors to assemble the 80S ribosomal initiation complex. Loss of translation control may result in cell malignant transformation. Here, we asked whether translational initiation factors could be regulated by NF-κB transcription factor, a major regulator of genes involved in cell proliferation, survival, and inflammatory response. We show that the p65 subunit of NF-κB activates the transcription of eIF4H gene, which is the regulatory subunit of eIF4A, the most relevant RNA helicase in translation initiation. The p65-dependent transcriptional activation of eIF4H increased the eIF4H protein content augmenting the rate of global protein synthesis. In this context, our results provide novel insights into protein synthesis regulation in response to NF-κB activation signalling, suggesting a transcription-translation coupled mechanism of control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Chromatin Immunoprecipitation
  • Eukaryotic Initiation Factor-4A / genetics
  • Eukaryotic Initiation Factor-4A / metabolism*
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology
  • HeLa Cells
  • Humans
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism*
  • Transcriptional Activation / genetics
  • Transcriptional Activation / physiology

Substances

  • Transcription Factor RelA
  • Eukaryotic Initiation Factor-4A

Grants and funding

This work was granted by Ministero dell’Istruzione, dell’Università e della Ricerca (PON01_02782 and PON01_00862); Ministero della Salute (RF-2010-2306943 and GR-2009-1606801); Associazione Italiana per la Ricerca sul Cancro (IG-2009-9411). A.R. and E.V. were supported by fellowships from Fondazione Italiana per la Ricerca sul Cancro. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.