Andersson, Robin

Bornholdt, Jette

Chen, Yun

Core, Leighton

Jensen, Torben Heick

Karadoulama, Evdoxia

Llinares, Marta Lloret

Sandelin, Albin

Villafano, Geno J

Wojenski, Luke A

English

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.</p

Copenhagen University Research Information System

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

https://curis.ku.dk/portal/files/212501094/The_RNA_exosome_contributes_to_gene_expression_regulation_during_stem_cell_differentiation.pdf

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

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Copenhagen University Research Information System