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

Marta Lloret Llinares; Evdoxia Karadoulama; Yun Chen; Luke A Wojenski; Geno J Villafano; Jette Bornholdt; Robin Andersson; Leighton Core; Albin Sandelin; Torben Heick Jensen

doi:10.1093/nar/gky817

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

Marta Lloret Llinares, Evdoxia Karadoulama, Yun Chen, Luke A Wojenski, Geno J Villafano, Jette Bornholdt, Robin Andersson, Leighton Core, Albin Sandelin, Torben Heick Jensen

Computational and RNA Biology

19 Citations (Scopus)

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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.

Original language	English
Journal	Nucleic Acids Research
Volume	46
Issue number	21
Pages (from-to)	11502-11513
ISSN	0305-1048
DOIs	https://doi.org/10.1093/nar/gky817
Publication status	Published - 30 Nov 2018

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The RNA exosome contributes to gene expression regulation during stem cell differentiationFinal published version, 1.83 MBLicence: CC BY

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title = "The RNA exosome contributes to gene expression regulation during stem cell differentiation",

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.",

author = "Llinares, {Marta Lloret} and Evdoxia Karadoulama and Yun Chen and Wojenski, {Luke A} and Villafano, {Geno J} and Jette Bornholdt and Robin Andersson and Leighton Core and Albin Sandelin and Jensen, {Torben Heick}",

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T1 - The RNA exosome contributes to gene expression regulation during stem cell differentiation

AU - Llinares, Marta Lloret

AU - Karadoulama, Evdoxia

AU - Chen, Yun

AU - Wojenski, Luke A

AU - Villafano, Geno J

AU - Bornholdt, Jette

AU - Andersson, Robin

AU - Core, Leighton

AU - Sandelin, Albin

AU - Jensen, Torben Heick

PY - 2018/11/30

Y1 - 2018/11/30

N2 - 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.

AB - 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.

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DO - 10.1093/nar/gky817

M3 - Journal article

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SN - 0305-1048

VL - 46

SP - 11502

EP - 11513

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 21

ER -

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

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