Nudt21 Controls Cell Fate by Connecting Alternative Polyadenylation to Chromatin Signaling

Cell. 2018 Jan 11;172(1-2):106-120.e21. doi: 10.1016/j.cell.2017.11.023. Epub 2017 Dec 14.


Cell fate transitions involve rapid gene expression changes and global chromatin remodeling, yet the underlying regulatory pathways remain incompletely understood. Here, we identified the RNA-processing factor Nudt21 as a novel regulator of cell fate change using transcription-factor-induced reprogramming as a screening assay. Suppression of Nudt21 enhanced the generation of induced pluripotent stem cells, facilitated transdifferentiation into trophoblast stem cells, and impaired differentiation of myeloid precursors and embryonic stem cells, suggesting a broader role for Nudt21 in cell fate change. We show that Nudt21 directs differential polyadenylation of over 1,500 transcripts in cells acquiring pluripotency, although only a fraction changed protein levels. Remarkably, these proteins were strongly enriched for chromatin regulators, and their suppression neutralized the effect of Nudt21 during reprogramming. Collectively, our data uncover Nudt21 as a novel post-transcriptional regulator of cell fate and establish a direct, previously unappreciated link between alternative polyadenylation and chromatin signaling.

Keywords: Alternative polyadenylation; chromatin; embryonic stem cells; epigenetic regulation; induced pluripotent stem cells; induced trophoblast stem cells; microRNA; pluripotency; reprogramming; transdifferentiation.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • Cellular Reprogramming*
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly*
  • Cleavage And Polyadenylation Specificity Factor / genetics
  • Cleavage And Polyadenylation Specificity Factor / metabolism*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • HEK293 Cells
  • Humans
  • Mice
  • Polyadenylation*
  • Signal Transduction*


  • Chromatin
  • Cleavage And Polyadenylation Specificity Factor
  • Nudt21 protein, mouse