Journal
EMBO REPORTS
Volume 16, Issue 10, Pages 1334-1357Publisher
WILEY
DOI: 10.15252/embr.201540974
Keywords
embryonic stem cells; makorin-1; RNA metabolism; stress granules
Categories
Funding
- Canadian Institutes for Health Research [MOP-89910, EPS-129130]
- Natural Sciences and Engineering Research Council [RGPIN 293170-11]
- CIHR Banting and Best CGS Doctoral Research Award
- Government of Ontario Ministry of Economic Development and Innovation for the Ontario Research Fund supporting the International Regulome Consortium
- Tier 1 Canada Research Chair in Integrative Stem Cell Biology
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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.
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