Critical Roles of Translation Initiation and RNA Uridylation in Endogenous Retroviral Expression and Neural Differentiation in Pluripotent Stem Cells

Cell Rep. 2020 Jun 2;31(9):107715. doi: 10.1016/j.celrep.2020.107715.


Previous studies have suggested that the loss of the translation initiation factor eIF4G1 homolog NAT1 induces excessive self-renewability of naive pluripotent stem cells (PSCs); yet the role of NAT1 in the self-renewal and differentiation of primed PSCs is still unclear. Here, we generate a conditional knockout of NAT1 in primed PSCs and use the cells for the functional analyses of NAT1. Our results show that NAT1 is required for the self-renewal and neural differentiation of primed PSCs. In contrast, NAT1 deficiency in naive pluripotency attenuates the differentiation to all cell types. We also find that NAT1 is involved in efficient protein expression of an RNA uridyltransferase, TUT7. TUT7 is involved in the neural differentiation of primed PSCs via the regulation of human endogenous retrovirus accumulation. These data demonstrate the essential roles of NAT1 and TUT7 in the precise transition of stem cell fate.

Keywords: endogenous retrovirus; neural differentiation; pluripotency; translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arylamine N-Acetyltransferase / deficiency
  • Arylamine N-Acetyltransferase / genetics
  • Arylamine N-Acetyltransferase / metabolism
  • Cell Differentiation*
  • Cell Line
  • Cell Lineage
  • Cell Self Renewal
  • Endogenous Retroviruses / genetics
  • Endogenous Retroviruses / metabolism*
  • Gene Editing
  • Humans
  • Isoenzymes / deficiency
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Mice
  • Neurons / cytology*
  • Neurons / metabolism
  • Peptide Chain Initiation, Translational
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • RNA Interference
  • RNA Nucleotidyltransferases / genetics
  • RNA Nucleotidyltransferases / metabolism
  • RNA, Small Interfering / metabolism
  • RNA, Viral / antagonists & inhibitors
  • RNA, Viral / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Isoenzymes
  • RNA, Small Interfering
  • RNA, Viral
  • Transcription Factors
  • Arylamine N-Acetyltransferase
  • N-acetyltransferase 1
  • RNA Nucleotidyltransferases
  • TUT7 protein, human