Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 17, Pages E1740-E1748Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1320873111
Keywords
stem cell biology; AU-rich element RNA-binding proteins; developmental mechanisms; developmental signaling pathways; gene regulation dynamics
Categories
Funding
- Human Frontiers Science Program Grant [RGP0020/2012]
- Weston Havens Foundation
- David and Lucille Packard Foundation
- National Defense Science and Engineering Graduate Research Fellowship
Ask authors/readers for more resources
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 post-transcriptional control of gene expression in mESCs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available