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Integrative genomics positions MKRN 1 as a novel ribonucleoprotein within the embryonic stem cell gene regulatory network
Author(s) -
Cassar Paul A,
Carpenedo Richard L,
SamavarchiTehrani Payman,
Olsen Jonathan B,
Park Chang Jun,
Chang Wing Y,
Chen Zhaoyi,
Choey Chandarong,
Delaney Sean,
Guo Huishan,
Guo Hongbo,
Tanner R Matthew,
Perkins Theodore J,
Tenenbaum Scott A,
Emili Andrew,
Wrana Jeffrey L,
Gibbings Derrick,
Stanford William L
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201540974
Subject(s) - embryonic stem cell , ribonucleoprotein , biology , genomics , gene , stem cell , genetics , gene regulatory network , computational biology , microbiology and biotechnology , genome , gene expression , rna
In embryonic stem cells ( ESC s), gene regulatory networks ( GRN s) 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 ( MKRN 1) as a potential novel component of the ESC GRN . Here, using multilayered systems‐level analyses, we compiled a MKRN 1‐centered interactome in undifferentiated ESC s at the proteomic and ribonomic level. Proteomic analyses in undifferentiated ESC s revealed that MKRN 1 associates with RNA ‐binding proteins, and ensuing RIP‐chip analysis determined that MKRN 1 associates with m RNA s encoding functionally related proteins including proteins that function during cellular stress. Subsequent biological validation identified MKRN 1 as a novel stress granule‐resident protein, although MKRN 1 is not required for stress granule formation, or survival of unstressed ESC s. Thus, our unbiased systems‐level analyses support a role for the E3 ligase MKRN 1 as a ribonucleoprotein within the ESC GRN .