| APPEL, Lisa-Marie, Vedran FRANKE, Melania BRUNO, Irina GRISHKOVSKAYA, Aiste KASILIAUSKAITE, Tanja KAUFMANN, Ursula E. SCHOEBERL, Martin G. PUCHINGER, Sebastian KOSTRHON, Carmen EBENWALDNER, Marek ŠEBESTA, Etienne BELTZUNG, Karl MECHTLER, Gen LIN, Anna VLASOVA, Martin LEEB, Rushad PAVRI, Alexander STARK, Altuna AKALIN, Richard ŠTEFL, Carrie BERNECKY, Kristina DJINOVIC-CARUGO a Dea SLADE. PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC. Nature Communications. London: Nature Publishing Group, roč. 12, č. 1, s. 6078-6101. ISSN 2041-1723. doi:10.1038/s41467-021-26360-2. 2021. |
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@article{1838578,
author = {Appel, LisaandMarie and Franke, Vedran and Bruno, Melania and Grishkovskaya, Irina and Kasiliauskaite, Aiste and Kaufmann, Tanja and Schoeberl, Ursula E. and Puchinger, Martin G. and Kostrhon, Sebastian and Ebenwaldner, Carmen and Šebesta, Marek and Beltzung, Etienne and Mechtler, Karl and Lin, Gen and Vlasova, Anna and Leeb, Martin and Pavri, Rushad and Stark, Alexander and Akalin, Altuna and Štefl, Richard and Bernecky, Carrie and DjinovicandCarugo, Kristina and Slade, Dea},
article_location = {London},
article_number = {1},
doi = {http://dx.doi.org/10.1038/s41467-021-26360-2},
keywords = {Gene expression; Neural stem cells; Transcription; X-ray crystallography},
language = {eng},
issn = {2041-1723},
journal = {Nature Communications},
title = {PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC},
url = {https://www.nature.com/articles/s41467-021-26360-2},
volume = {12},
year = {2021}
}
TY - JOUR
ID - 1838578
AU - Appel, Lisa-Marie - Franke, Vedran - Bruno, Melania - Grishkovskaya, Irina - Kasiliauskaite, Aiste - Kaufmann, Tanja - Schoeberl, Ursula E. - Puchinger, Martin G. - Kostrhon, Sebastian - Ebenwaldner, Carmen - Šebesta, Marek - Beltzung, Etienne - Mechtler, Karl - Lin, Gen - Vlasova, Anna - Leeb, Martin - Pavri, Rushad - Stark, Alexander - Akalin, Altuna - Štefl, Richard - Bernecky, Carrie - Djinovic-Carugo, Kristina - Slade, Dea
PY - 2021
TI - PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC
JF - Nature Communications
VL - 12
IS - 1
SP - 6078
EP - 6078
PB - Nature Publishing Group
SN - 20411723
KW - Gene expression
KW - Neural stem cells
KW - Transcription
KW - X-ray crystallography
UR - https://www.nature.com/articles/s41467-021-26360-2
N2 - 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. Here the authors identify PHF3 SPOC domain as a reader of the phosphorylated RNA polymerase II (Pol II) C-terminal domain. They show that PHF3 clusters with Pol II complexes in cells, drives phase separation of Pol II in vitro, and regulates neuronal gene expression and neuronal differentiation.
ER -
APPEL, Lisa-Marie, Vedran FRANKE, Melania BRUNO, Irina GRISHKOVSKAYA, Aiste KASILIAUSKAITE, Tanja KAUFMANN, Ursula E. SCHOEBERL, Martin G. PUCHINGER, Sebastian KOSTRHON, Carmen EBENWALDNER, Marek ŠEBESTA, Etienne BELTZUNG, Karl MECHTLER, Gen LIN, Anna VLASOVA, Martin LEEB, Rushad PAVRI, Alexander STARK, Altuna AKALIN, Richard ŠTEFL, Carrie BERNECKY, Kristina DJINOVIC-CARUGO a Dea SLADE. PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC. \textit{Nature Communications}. London: Nature Publishing Group, roč.~12, č.~1, s.~6078-6101. ISSN~2041-1723. doi:10.1038/s41467-021-26360-2. 2021.
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