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| Nature communications. 2021 Oct 19. doi: 10.1038/s41467-021-26360-2. pii: 10.1038/s41467-021-26360-2 |
| PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC. |
| Appel LM1, Franke V2, Bruno M3, Grishkovskaya I4, Kasiliauskaite A5, Kaufmann T6, Schoeberl UE7, Puchinger MG8, Kostrhon S9, Ebenwaldner C10, Sebesta M11, Beltzung E12, Mechtler K13, Lin G14, Vlasova A15, Leeb M16, Pavri R17, Stark A18, Akalin A19, Stefl R20, Bernecky C21, Djinovic-Carugo K22, Slade D23 |
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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. |
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© 2021. The Author(s). |
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Publikations ID: 34667177 Quelle: öffnen |
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