Brf1 posttranscriptionally regulates pluripotency and differentiation responses downstream of Erk MAP kinase
| Autor: | Frederick E. Tan, Michael B. Elowitz |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Pluripotent Stem Cells
Homeobox protein NANOG Transcription Genetic MAP Kinase Signaling System Cellular differentiation Cell fate determination Biology Response Elements Fibroblast growth factor Mesoderm Mice Tristetraprolin Animals RNA Messenger Extracellular Signal-Regulated MAP Kinases Induced pluripotent stem cell Embryonic Stem Cells Cell Proliferation AU Rich Elements Homeodomain Proteins Regulation of gene expression Multidisciplinary Primitive streak Endoderm Nuclear Proteins RNA-Binding Proteins Cell Differentiation Nanog Homeobox Protein Embryonic stem cell Cell biology Fibroblast Growth Factors PNAS Plus Gene Expression Regulation Butyrate Response Factor 1 Half-Life Protein Binding |
| Popis: | AU-rich element mRNA-binding proteins (AUBPs) are key regulators of development, but how they are controlled and what functional roles they play depends on cellular context. Here, we show that Brf1 (zfp36l1), an AUBP from the Zfp36 protein family, operates downstream of FGF/Erk MAP kinase signaling to regulate pluripotency and cell fate decision making in mouse embryonic stem cells (mESCs). FGF/Erk MAP kinase signaling up-regulates Brf1, which disrupts the expression of core pluripotency-associated genes and attenuates mESC self-renewal without inducing differentiation. These regulatory effects are mediated by rapid and direct destabilization of Brf1 targets, such as Nanog mRNA. Enhancing Brf1 expression does not compromise mESC pluripotency but does preferentially regulate mesendoderm commitment during differentiation, accelerating the expression of primitive streak markers. Together, these studies demonstrate that FGF signals use targeted mRNA degradation by Brf1 to enable rapid posttranscriptional control of gene expression in mESCs. |
| Databáze: | OpenAIRE |
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