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A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening
Published on: May 12, 2017
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Noncanonical function of DGCR8 controls mESC exit from pluripotency
Daniel Cirera-Salinas1, Jian Yu1,2, Maxime Bodak1,2
1Department of Biology, Institute of Molecular Health Sciences, RNAi and Genome Integrity, Swiss Federal Institute of Technology Zurich, Zurich 8093, Switzerland.
The Journal of Cell Biology
|January 20, 2017
Summary
DGCR8 is crucial for mouse stem cell differentiation, controlling pluripotency exit. Beyond microRNA processing, DGCR8 regulates Tcf7l1 splicing, a key step for stem cell differentiation.
Area of Science:
- Stem cell biology
- Molecular genetics
- RNA biology
Background:
- Mouse embryonic stem cells (mESCs) lacking DGCR8 exhibit differentiation defects.
- The precise mechanisms behind these pluripotency commitment failures are not fully understood.
Purpose of the Study:
- To elucidate the role of DGCR8 in mESC differentiation and pluripotency exit.
- To differentiate between canonical and noncanonical functions of DGCR8.
Main Methods:
- Generation and analysis of DGCR8-deficient mESCs.
- Complementation with a phosphomutant DGCR8.
- Integration of omics data and RNA immunoprecipitation (RIP).
Main Results:
- DGCR8 is essential for exiting the pluripotent state in mESCs.
- A phosphomutant DGCR8 restored microRNA levels but not pluripotency exit.
- DGCR8 directly interacts with Tcf7l1 mRNA, a pluripotency factor.
- DGCR8 facilitates Tcf7l1 splicing, which is critical for mESC differentiation.
Conclusions:
- DGCR8 plays a noncanonical role in modulating alternative splicing of Tcf7l1 mRNA.
- This splicing function is independent of its established role in microRNA biogenesis.
- DGCR8 is vital for regulating stem cell differentiation through alternative splicing.
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