Integrative genomics positions MKRN1 as a novel ribonucleoprotein within the embryonic stem cell gene regulatory network

EMBO Rep. 2015 Oct;16(10):1334-57. doi: 10.15252/embr.201540974. Epub 2015 Aug 11.


In embryonic stem cells (ESCs), gene regulatory networks (GRNs) coordinate gene expression to maintain ESC identity; however, the complete repertoire of factors regulating the ESC state is not fully understood. Our previous temporal microarray analysis of ESC commitment identified the E3 ubiquitin ligase protein Makorin-1 (MKRN1) as a potential novel component of the ESC GRN. Here, using multilayered systems-level analyses, we compiled a MKRN1-centered interactome in undifferentiated ESCs at the proteomic and ribonomic level. Proteomic analyses in undifferentiated ESCs revealed that MKRN1 associates with RNA-binding proteins, and ensuing RIP-chip analysis determined that MKRN1 associates with mRNAs encoding functionally related proteins including proteins that function during cellular stress. Subsequent biological validation identified MKRN1 as a novel stress granule-resident protein, although MKRN1 is not required for stress granule formation, or survival of unstressed ESCs. Thus, our unbiased systems-level analyses support a role for the E3 ligase MKRN1 as a ribonucleoprotein within the ESC GRN.

Keywords: RNA metabolism; embryonic stem cells; makorin‐1; stress granules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytoplasm / metabolism
  • Embryonic Stem Cells / physiology*
  • Gene Regulatory Networks / genetics*
  • Genomics
  • Mice
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics*
  • Proteomics
  • RNA / metabolism
  • RNA-Binding Proteins / metabolism
  • Ribonucleoproteins / chemistry
  • Ribonucleoproteins / genetics*
  • Ubiquitin-Protein Ligases / metabolism


  • Makorin ring finger protein 1
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • RNA
  • Ubiquitin-Protein Ligases

Associated data

  • GEO/GSE59394