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PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC

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Item Type:Article
Title:PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC
Creators Name:Appel, L.M. and Franke, V. and Bruno, M. and Grishkovskaya, I. and Kasiliauskaite, A. and Kaufmann, T. and Schoeberl, U.E. and Puchinger, M.G. and Kostrhon, S. and Ebenwaldner, C. and Sebesta, M. and Beltzung, E. and Mechtler, K. and Lin, G. and Vlasova, A. and Leeb, M. and Pavri, R. and Stark, A. and Akalin, A. and Stefl, R. and Bernecky, C. and Djinovic-Carugo, K. and Slade, D.
Abstract:The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is a regulatory hub for transcription and RNA processing. Here, we identify PHD-finger protein 3 (PHF3) as a regulator of transcription and mRNA stability that docks onto Pol II CTD through its SPOC domain. We characterize SPOC as a CTD reader domain that preferentially binds two phosphorylated Serine-2 marks in adjacent CTD repeats. PHF3 drives liquid-liquid phase separation of phosphorylated Pol II, colocalizes with Pol II clusters and tracks with Pol II across the length of genes. PHF3 knock-out or SPOC deletion in human cells results in increased Pol II stalling, reduced elongation rate and an increase in mRNA stability, with marked derepression of neuronal genes. Key neuronal genes are aberrantly expressed in Phf3 knock-out mouse embryonic stem cells, resulting in impaired neuronal differentiation. Our data suggest that PHF3 acts as a prominent effector of neuronal gene regulation by bridging transcription with mRNA decay.
Keywords:Animals, Drosophila melanogaster, Mice
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:12
Number:1
Page Range:6078
Date:19 October 2021
Official Publication:https://doi.org/10.1038/s41467-021-26360-2
PubMed:View item in PubMed
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https://edoc.mdc-berlin.de/18792/Preprint version

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