Repression of global protein synthesis by Eif1a-like genes that are expressed specifically in the two-cell embryos and the transient Zscan4-positive state of embryonic stem cells

DNA Res. 2013 Aug;20(4):391-402. doi: 10.1093/dnares/dst018. Epub 2013 May 5.


Mouse embryonic stem (ES) cells are prototypical stem cells that remain undifferentiated in culture for long periods, yet maintain the ability to differentiate into essentially all cell types. Previously, we have reported that ES cells oscillate between two distinct states, which can be distinguished by the transient expression of Zscan4 genes originally identified for its specific expression in mouse two-cell stage embryos. Here, we report that the nascent protein synthesis is globally repressed in the Zscan4-positive state of ES cells, which is mediated by the transient expression of newly identified eukaryotic translation initiation factor 1A (Eif1a)-like genes. Eif1a-like genes, clustered on Chromosome 12, show the high sequence similarity to the Eifa1 and consist of 10 genes (Eif1al1-Eif1al10) and 9 pseudogenes (Eif1al-ps1-Eif1al-ps9). The analysis of the expressed sequence tag database showed that Eif1a-like genes are expressed mostly in the two-cell stage mouse embryos. Microarray analyses and quantitative real-time polymerase chain reaction analyses show that Eif1a-like genes are expressed specifically in the Zscan4-positive state of ES cells. These results indicate a novel mechanism to repress protein synthesis by Eif1a-like genes and a unique mode of protein synthesis regulation in ES cells, which undergo a transient and reversible repression of global protein synthesis in the Zscan4-positive state.

Keywords: Eif1a-like genes; Zscan4; embryonic stem cell; global translational repression; two-cell stage embryo.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Chromosomes, Mammalian
  • Embryo, Mammalian
  • Embryonic Stem Cells / classification
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Eukaryotic Initiation Factor-1 / classification
  • Eukaryotic Initiation Factor-1 / genetics*
  • Eukaryotic Initiation Factor-1 / metabolism
  • Expressed Sequence Tags
  • Gene Expression Regulation, Developmental*
  • Mice
  • Multigene Family
  • Protein Biosynthesis*
  • Protein Isoforms / classification
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Eukaryotic Initiation Factor-1
  • Protein Isoforms
  • Transcription Factors
  • Zscan4d protein, mouse
  • Zscan4f protein, mouse
  • eukaryotic peptide initiation factor-1A