Uncovering the RNA-binding protein landscape in the pluripotency network of human embryonic stem cells

Shlomi Dvir, Amir Argoetti, Chen Lesnik, Mark Roytblat, Kohava Shriki, Michal Amit, Tamar Hashimshony, Yael Mandel-Gutfreund

Research output: Contribution to journalArticlepeer-review


Embryonic stem cell (ESC) self-renewal and cell fate decisions are driven by a broad array of molecular signals. While transcriptional regulators have been extensively studied in human ESCs (hESCs), the extent to which RNA-binding proteins (RBPs) contribute to human pluripotency remains unclear. Here, we carry out a proteome-wide screen and identify 810 proteins that bind RNA in hESCs. We reveal that RBPs are preferentially expressed in hESCs and dynamically regulated during early stem cell differentiation. Notably, many RBPs are affected by knockdown of OCT4, a master regulator of pluripotency, several dozen of which are directly targeted by this factor. Using cross-linking and immunoprecipitation (CLIP-seq), we find that the pluripotency-associated STAT3 and OCT4 transcription factors interact with RNA in hESCs and confirm the binding of STAT3 to the conserved NORAD long-noncoding RNA. Our findings indicate that RBPs have a more widespread role in human pluripotency than previously appreciated.

Original languageEnglish
Article number109198
JournalCell Reports
Issue number9
StatePublished - 1 Jun 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 The Author(s)


  • DNA- and RNA-binding proteins
  • DRBPs
  • RBPs
  • RNA interactome capture
  • RNA-binding proteins
  • STAT3-RNA interaction
  • hESCs
  • human embryonic stem cells
  • pluripotency network
  • post-transcriptional regulation

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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