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

• DOI: 10.1038/s41467-021-26360-2
• Publication Date: 2021-10-19T10:04:50Z
• Authors: 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...; Dea Slade
• Keywords: CTD

The C-terminal domain (CTD) of the largest subunit RNA polymerase II (Pol II) is a regulatory hub for transcription and processing. Here, we identify PHD-finger protein 3 (PHF3) as regulator mRNA stability that docks onto Pol CTD through its SPOC domain. We characterize reader preferentially binds two phosphorylated Serine-2 marks in adjacent repeats. PHF3 drives liquid-liquid phase separation II, colocalizes with clusters tracks across length genes. knock-out or deletion human cells results increased stalling, reduced elongation rate an increase stability, marked derepression neuronal Key genes are aberrantly expressed Phf3 mouse embryonic stem cells, resulting impaired differentiation. Our data suggest acts prominent effector gene regulation by bridging decay.