Dicer, a new regulator of pluripotency exit and LINE-1 elements in mouse embryonic stem cells.
A gene regulation network orchestrates processes ensuring the maintenance of cellular identity and genome integrity. Small RNAs generated by the RNAse III DICER have emerged as central players in this network. Moreover, deletion ofDicerin mice leads to early embryonic lethality. To better understand the underlying mechanisms leading to this phenotype, we generatedDicer-deficient mouse embryonic stem cells (mESCs). Their detailed characterization revealed an impaired differentiation potential, and incapacity to exit from the pluripotency state. We also observed a strong accumulation of LINE-1 (L1s) transcripts, which was translated at protein level and led to an increased L1s retrotransposition. Our findings revealDiceras a new essential player that sustains mESCs self-renewal and genome integrity by controlling L1s regulation.
Department of Biology RNAi and Genome Integrity IMHS Swiss Federal Institute of Technology Zurich Zurich Switzerland; Life Science Zurich Graduate School Molecular Life Science Program University of Zurich Switzerland.
Maxime
M
Bodak
Department of Biology RNAi and Genome Integrity IMHS Swiss Federal Institute of Technology Zurich Zurich Switzerland.
Daniel
D
Cirera-Salinas
Department of Biology RNAi and Genome Integrity IMHS Swiss Federal Institute of Technology Zurich Zurich Switzerland; Life Science Zurich Graduate School Molecular and Translational Biomedicine Program University of Zurich Switzerland.
Jian
J
Yu
Department of Biology RNAi and Genome Integrity IMHS Swiss Federal Institute of Technology Zurich Zurich Switzerland.
Richard P
RP
Ngondo
Department of Biology RNAi and Genome Integrity IMHS Swiss Federal Institute of Technology Zurich Zurich Switzerland.
Constance
C
Ciaudo
Dicer; LINE‐1 retrotransposition; mouse embryonic stem cells; transposable elements