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The RNA exosome contributes to gene expression regulation during stem cell differentiation

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  • Marta Lloret-Llinares
  • ,
  • Evdoxia Karadoulama, University of Copenhagen
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  • Yun Chen, University of Copenhagen
  • ,
  • Luke A Wojenski, Department of Molecular and Cell Biology, Institute for Systems Genomics, University of Connecticut, Storrs, CT, USA.
  • ,
  • Geno J Villafano, Department of Molecular and Cell Biology, Institute for Systems Genomics, University of Connecticut, Storrs, CT, USA.
  • ,
  • Jette Bornholdt, University of Copenhagen
  • ,
  • Robin Andersson, The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  • ,
  • Leighton Core, Department of Molecular and Cell Biology, Institute for Systems Genomics, University of Connecticut, Storrs, CT, USA.
  • ,
  • Albin Sandelin, University of Copenhagen
  • ,
  • Torben Heick Jensen

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.

Original languageEnglish
JournalNucleic Acids Research
Volume46
Issue21
Pages (from-to)11502-11513
Number of pages12
ISSN0305-1048
DOIs
Publication statusPublished - 30 Nov 2018

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