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

Lisa-Marie Appel, Vedran Franke, Melania Bruno, Irina Grishkovskaya, Aiste Kasiliauskaite, Tanja Kaufmann, Ursula E. Schoeberl, Martin G. Puchinger, Sebastian Kostrhon, Carmen Ebenwaldner, Marek Sebesta, Etienne Beltzung, Karl Mechtler, Gen Lin, Anna Vlasova, Martin Leeb, Rushad Pavri, Alexander Stark, Altuna Akalin, Richard Stefl, Carrie Bernecky, Kristina Djinovic-Carugo and Dea Slade ()
Additional contact information
Lisa-Marie Appel: University of Vienna, Vienna Biocenter (VBC)
Vedran Franke: Max Delbrück Center
Melania Bruno: University of Vienna, Vienna Biocenter (VBC)
Irina Grishkovskaya: University of Vienna, Vienna Biocenter (VBC)
Aiste Kasiliauskaite: Masaryk University
Tanja Kaufmann: University of Vienna, Vienna Biocenter (VBC)
Ursula E. Schoeberl: Masaryk University
Martin G. Puchinger: University of Vienna, Vienna Biocenter (VBC)
Sebastian Kostrhon: University of Vienna, Vienna Biocenter (VBC)
Carmen Ebenwaldner: University of Vienna, Vienna Biocenter (VBC)
Marek Sebesta: Masaryk University
Etienne Beltzung: University of Vienna, Vienna Biocenter (VBC)
Karl Mechtler: Vienna Biocenter (VBC)
Gen Lin: Vienna Biocenter (VBC)
Anna Vlasova: Vienna Biocenter (VBC)
Martin Leeb: University of Vienna, Vienna Biocenter (VBC)
Rushad Pavri: Vienna Biocenter (VBC)
Alexander Stark: Vienna Biocenter (VBC)
Altuna Akalin: Max Delbrück Center
Richard Stefl: Masaryk University
Carrie Bernecky: Institute of Science and Technology Austria (IST Austria), Am Campus 1
Kristina Djinovic-Carugo: University of Vienna, Vienna Biocenter (VBC)
Dea Slade: University of Vienna, Vienna Biocenter (VBC)

Nature Communications, 2021, vol. 12, issue 1, 1-24

Abstract: 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.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-26360-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26360-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-26360-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().