The RNA exosome contributes to gene expression regulation during stem cell differentiation
Open Access
- 13 September 2018
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 46 (21), 11502-11513
- https://doi.org/10.1093/nar/gky817
Abstract
Gene expression programs change during cellular transitions. It is well established that a network of transcription factors and chromatin modifiers regulate RNA levels during embryonic stem cell (ESC) differentiation, but the full impact of post-transcriptional processes remains elusive. While cytoplasmic RNA turnover mechanisms have been implicated in differentiation, the contribution of nuclear RNA decay has not been investigated. Here, we differentiate mouse ESCs, depleted for the ribonucleolytic RNA exosome, into embryoid bodies to determine to which degree RNA abundance in the two states can be attributed to changes in transcription versus RNA decay by the exosome. As a general observation, we find that exosome depletion mainly leads to the stabilization of RNAs from lowly transcribed loci, including several protein-coding genes. Depletion of the nuclear exosome cofactor RBM7 leads to similar effects. In particular, transcripts that are differentially expressed between states tend to be more exosome sensitive in the state where expression is low. We conclude that the RNA exosome contributes to down-regulation of transcripts with disparate expression, often in conjunction with transcriptional down-regulation.Keywords
Funding Information
- European Research Council (339953)
- Danish Council for Independent Research (DFF-1333-00059B)
This publication has 85 references indexed in Scilit:
- Threading the barrel of the RNA exosomeTrends in Biochemical Sciences, 2013
- Landscape of transcription in human cellsNature, 2012
- Pumilio 1 Suppresses Multiple Activators of p53 to Safeguard SpermatogenesisCurrent Biology, 2012
- lincRNAs act in the circuitry controlling pluripotency and differentiationNature, 2011
- Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cellsNature Biotechnology, 2011
- Control of the Embryonic Stem Cell StateCell, 2011
- Importance of polyadenylation in the selective elimination of meiotic mRNAs in growing S. pombe cellsThe EMBO Journal, 2010
- The Many Pathways of RNA DegradationCell, 2009
- Wnt Signaling Mediates Self-Organization and Axis Formation in Embryoid BodiesCell Stem Cell, 2008
- The ground state of embryonic stem cell self-renewalNature, 2008