| Literature DB >> 34667177 |
Lisa-Marie Appel1, Vedran Franke2, Melania Bruno1, Irina Grishkovskaya3, Aiste Kasiliauskaite4,5, Tanja Kaufmann1, Ursula E Schoeberl5, Martin G Puchinger3, Sebastian Kostrhon1, Carmen Ebenwaldner1, Marek Sebesta4, Etienne Beltzung1, Karl Mechtler6,7, Gen Lin6, Anna Vlasova6, Martin Leeb8, Rushad Pavri6, Alexander Stark6, Altuna Akalin2, Richard Stefl4,5, Carrie Bernecky9, Kristina Djinovic-Carugo3,10, Dea Slade11,12,13.
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.Entities:
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Year: 2021 PMID： 34667177 PMCID： PMC8526623 DOI： 10.1038/s41467-021-26360-2
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919