title: The Role of RNA Interference in Stem Cell Biology: Beyond the Mutant Phenotypes.
abstract: Complex gene regulation systems ensure the maintenance of cellular identity during early development in mammals. Eukaryotic small RNAs have emerged as critical players in RNA interference (RNAi) by mediating gene silencing during embryonic stem cell self-renewal. Most of the proteins involved in the biogenesis of small RNAs are essential for proliferation and differentiation into the three germ layers of mouse embryonic stem cells. In the last decade, new functions for some RNAi proteins, independent of their roles in RNAi pathways, have been demonstrated in different biological systems. In parallel, new concepts in stem cell biology have emerged. Here, we review and integrate the current understanding of how RNAi proteins regulate stem cell identity with the new advances in the stem cell field and the recent non-canonical functions of the RNAi proteins. Finally, we propose a reevaluation of all RNAi mutant phenotypes, as non-canonical (small non-coding RNA independent) functions may contribute to the molecular mechanisms governing mouse embryonic stem cells commitment.
authors.affiliation: Swiss Federal Institute of Technology Zurich, Department of Biology, Institute of Molecular Health Sciences, CH-8093 Zurich, Switzerland; Life Science Zurich Graduate School, Molecular Life Science program, University of Zurich, CH-8047 Zurich, Switzerland. Electronic address: maxime.bodak@biol.ethz.ch.
authors.forename: Maxime
authors.initials: M
authors.lastname: Bodak
authors.affiliation: Swiss Federal Institute of Technology Zurich, Department of Biology, Institute of Molecular Health Sciences, CH-8093 Zurich, Switzerland. Electronic address: daniel.cirera@biol.ethz.ch.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cirera-Salinas
authors.affiliation: Swiss Federal Institute of Technology Zurich, Department of Biology, Institute of Molecular Health Sciences, CH-8093 Zurich, Switzerland; Life Science Zurich Graduate School, RNA Biology program, University of Zurich, CH-8057 Zurich, Switzerland. Electronic address: janina.luitz@biol.ethz.ch.
authors.forename: Janina
authors.initials: J
authors.lastname: Luitz
authors.affiliation: Swiss Federal Institute of Technology Zurich, Department of Biology, Institute of Molecular Health Sciences, CH-8093 Zurich, Switzerland. Electronic address: cciaudo@ethz.ch.
authors.forename: Constance
authors.initials: C
authors.lastname: Ciaudo
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D034622:RNA Interference
keywords: RNA interference pathways; exit from pluripotency; mouse embryonic stem cells; non-canonical functions of RNAi proteins