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circZNF827 nucleates a transcription inhibitory complex to balance neuronal differentiation

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circZNF827 nucleates a transcription inhibitory complex to balance neuronal differentiation. / Hollensen, Anne Kruse; Thomsen, Henriette Sylvain; Lloret-Llinares, Marta; Kamstrup, Andreas Bjerregaard; Jensen, Jacob Malte; Luckmann, Majbritt; Birkmose, Nanna; Palmfeldt, Johan; Jensen, Torben Heick; Hansen, Thomas B; Damgaard, Christian Kroun.

In: eLife, Vol. 9, e58478, 11.2020.

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@article{06fbd87bbf8e4285847390acaa7e09e6,
title = "circZNF827 nucleates a transcription inhibitory complex to balance neuronal differentiation",
abstract = "Circular RNAs are important for many cellular processes but their mechanisms of action remain poorly understood. Here, we map circRNA inventories of mouse embryonic stem cells, neuronal progenitor cells and differentiated neurons and identify hundreds of highly expressed circRNAs. By screening several candidate circRNAs for a potential function in neuronal differentiation, we find that circZNF827 represses expression of key neuronal markers, suggesting that this molecule negatively regulates neuronal differentiation. Among 760 tested genes linked to known neuronal pathways, knockdown of circZNF827 deregulates expression of numerous genes including nerve growth factor receptor (NGFR), which becomes transcriptionally upregulated to enhance NGF signaling. We identify a circZNF827-nucleated transcription-repressive complex containing hnRNP-K/L proteins and show that knockdown of these factors strongly augments NGFR regulation. Finally, we show that the ZNF827 protein is part of the mRNP complex, suggesting a functional co-evolution of a circRNA and the protein encoded by its linear pre-mRNA host.",
author = "Hollensen, {Anne Kruse} and Thomsen, {Henriette Sylvain} and Marta Lloret-Llinares and Kamstrup, {Andreas Bjerregaard} and Jensen, {Jacob Malte} and Majbritt Luckmann and Nanna Birkmose and Johan Palmfeldt and Jensen, {Torben Heick} and Hansen, {Thomas B} and Damgaard, {Christian Kroun}",
note = "{\textcopyright} 2020, Hollensen et al.",
year = "2020",
month = nov,
doi = "10.7554/eLife.58478",
language = "English",
volume = "9",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

RIS

TY - JOUR

T1 - circZNF827 nucleates a transcription inhibitory complex to balance neuronal differentiation

AU - Hollensen, Anne Kruse

AU - Thomsen, Henriette Sylvain

AU - Lloret-Llinares, Marta

AU - Kamstrup, Andreas Bjerregaard

AU - Jensen, Jacob Malte

AU - Luckmann, Majbritt

AU - Birkmose, Nanna

AU - Palmfeldt, Johan

AU - Jensen, Torben Heick

AU - Hansen, Thomas B

AU - Damgaard, Christian Kroun

N1 - © 2020, Hollensen et al.

PY - 2020/11

Y1 - 2020/11

N2 - Circular RNAs are important for many cellular processes but their mechanisms of action remain poorly understood. Here, we map circRNA inventories of mouse embryonic stem cells, neuronal progenitor cells and differentiated neurons and identify hundreds of highly expressed circRNAs. By screening several candidate circRNAs for a potential function in neuronal differentiation, we find that circZNF827 represses expression of key neuronal markers, suggesting that this molecule negatively regulates neuronal differentiation. Among 760 tested genes linked to known neuronal pathways, knockdown of circZNF827 deregulates expression of numerous genes including nerve growth factor receptor (NGFR), which becomes transcriptionally upregulated to enhance NGF signaling. We identify a circZNF827-nucleated transcription-repressive complex containing hnRNP-K/L proteins and show that knockdown of these factors strongly augments NGFR regulation. Finally, we show that the ZNF827 protein is part of the mRNP complex, suggesting a functional co-evolution of a circRNA and the protein encoded by its linear pre-mRNA host.

AB - Circular RNAs are important for many cellular processes but their mechanisms of action remain poorly understood. Here, we map circRNA inventories of mouse embryonic stem cells, neuronal progenitor cells and differentiated neurons and identify hundreds of highly expressed circRNAs. By screening several candidate circRNAs for a potential function in neuronal differentiation, we find that circZNF827 represses expression of key neuronal markers, suggesting that this molecule negatively regulates neuronal differentiation. Among 760 tested genes linked to known neuronal pathways, knockdown of circZNF827 deregulates expression of numerous genes including nerve growth factor receptor (NGFR), which becomes transcriptionally upregulated to enhance NGF signaling. We identify a circZNF827-nucleated transcription-repressive complex containing hnRNP-K/L proteins and show that knockdown of these factors strongly augments NGFR regulation. Finally, we show that the ZNF827 protein is part of the mRNP complex, suggesting a functional co-evolution of a circRNA and the protein encoded by its linear pre-mRNA host.

U2 - 10.7554/eLife.58478

DO - 10.7554/eLife.58478

M3 - Journal article

C2 - 33174841

VL - 9

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e58478

ER -