The Sm protein methyltransferase PRMT5 is not required for primordial germ cell specification in mice

EMBO J. 2015 Mar 12;34(6):748-58. doi: 10.15252/embj.201489319. Epub 2014 Dec 17.


PRMT5 is a type II protein arginine methyltransferase with roles in stem cell biology, reprograming, cancer and neurogenesis. During embryogenesis in the mouse, it was hypothesized that PRMT5 functions with the master germline determinant BLIMP1 to promote primordial germ cell (PGC) specification. Using a Blimp1-Cre germline conditional knockout, we discovered that Prmt5 has no major role in murine germline specification, or the first global epigenetic reprograming event involving depletion of cytosine methylation from DNA and histone H3 lysine 9 dimethylation from chromatin. Instead, we discovered that PRMT5 functions at the conclusion of PGC reprograming I to promote proliferation, survival and expression of the gonadal germline program as marked by MVH. We show that PRMT5 regulates gene expression by promoting methylation of the Sm spliceosomal proteins and significantly altering the spliced repertoire of RNAs in mammalian embryonic cells and primordial cells.

Keywords: PGC specification; PRMT5; conditional knockout; germline absence; splicing.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation / physiology*
  • Computational Biology
  • DNA Methylation
  • DNA Primers / genetics
  • Epigenesis, Genetic / physiology*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental / physiology*
  • Gene Knockout Techniques
  • Genotype
  • Germ Cells / cytology*
  • Germ Cells / enzymology
  • Mice
  • Positive Regulatory Domain I-Binding Factor 1
  • Protein Methyltransferases / metabolism*
  • Protein-Arginine N-Methyltransferases
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, RNA
  • Spliceosomes / metabolism
  • Transcription Factors / genetics*


  • DNA Primers
  • Prdm1 protein, mouse
  • Transcription Factors
  • Positive Regulatory Domain I-Binding Factor 1
  • Protein Methyltransferases
  • Prmt5 protein, mouse
  • Protein-Arginine N-Methyltransferases