Haploinsufficiency screen highlights two distinct groups of ribosomal protein genes essential for embryonic stem cell fate

Haploinsufficiency Ribosomal protein
DOI: 10.1073/pnas.1418845112 Publication Date: 2015-02-03T04:18:45Z
ABSTRACT
In a functional genomics screen of mouse embryonic stem cells (ESCs) with nested hemizygous chromosomal deletions, we reveal that ribosomal protein (RP) genes are the most significant haploinsufficient determinants for embryoid body (EB) formation. Hemizygocity three RP (Rps5, Rps14, or Rps28), distinguished by proximity their corresponding to ribosome's mRNA exit site, is associated profound phenotype. This EB phenotype was fully rescued BAC cDNA complementation but not reduction p53 levels, although such effective other RP-deleted clones non-mRNA exit-site proteins. RNA-sequencing studies further revealed undifferentiated ESCs Rps5 showed reduced expression levels several mesoderm-specific as compared wild-type counterparts. Together, these results gene dosage limits differentiation, self-renewal, ESCs. They also highlight two separate mechanisms underlying this process, one which independent.
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