Spotlights
Regulation of transcription and RNA stability through RNA Pol II CTD
We identified PHF3 as a new transcription elongation factor that directly binds to Pol II CTD via the SPOC domain and regulates neuronal gene expression and neuronal differentiation.
SPOC is a versatile phosphoserine reader domain in gene expression regulation
SPOC domains of PHF3, DIDO, RBM15 and SPEN (SHARP) display different affinities and specificities for Pol II CTD phosphomarks. PHF3 and DIDO SPOC specifically recognize tandem pS2, whereas SPEN and RBM15 SPOC preferentially bind pS5. PHF3 and DIDO SPOC primarily mediate interactions with Pol II and the transcription elongation machinery, while RBM15 and SPEN SPOC bind writers and readers of m6A.
Transcriptional brothers
PHF3 and DIDO3 paralogues co-regulate transcription by bridging the Pol II elongation machinery with chromatin and RNA processing factors and tethering Pol II in a phase-separated microenvironment. In the absence of PHF3, the DIDO long isoform DIDO3, which contains the SPOC domain, is upregulated to compensate for PHF3 loss as an example of paralogue buffering through isoform switching.
The mechanism of PARG interaction with PCNA
We identified a non-canonical PIP-box in the disordered regulatory region of poly(ADP-ribose) glycohydrolase (PARG) as the PCNA binding motif and showed based on X-ray structure analysis that the PARG PIP-box interacts with PCNA via both hydrophobic and electrostatic interactions. PARG PIP-box is critical for PARG recruitment to DNA damage sites.
11:00
IMBA/GMI Lecture Hall
Dea Slade
Gaia Novarino