TY - JOUR T1 - Deimination of arginine at the C-terminal domain favors RNA polymerase II pause release JF - bioRxiv DO - 10.1101/216143 SP - 216143 AU - Priyanka Sharma AU - Antonios Lioutas AU - Javier Quilez AU - Roni H.G. Wright AU - Chiara Di Vona AU - Francois Le Dily AU - Roland Schüller AU - Dirk Eick AU - Miguel Beato Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/11/08/216143.abstract N2 - Summary The C-terminal domain of the large subunit of RNA polymerase II (RNAP2-CTD) coordinates transcription and associated processes by acting as a landing platform for a variety of protein complexes. In mammals, the RNAP2-CTD comprises 52 heptapeptide repeats, the first half of which (1-27) exhibit the consensus repeat sequence Y1-S2-P3-T4-S5-P6-S7, whereas the second half (28-52) contains deviations from this consensus 1–3. The residues present on CTD undergo posttranslational modifications to determine which factors will be recruited to process nascent transcripts and modify chromatin. Dynamic phosphorylation, mainly on serines 2 and 5 mediates selective recruitment of protein complexes 4–7, but recently, modifications of lysines and arginines in non-consensus repeats have expanded the functional complexity of the CTD code8–11. Here we show that R1810 can be deiminated by PADI2 favoring RNAP2 pause release at highly expressed genes relevant for proliferation of breast cancer cells. Depletion of PADI2 reduced expression of these genes accompanied by accumulation of RNAP2 at transcriptional start sites and resulted in inhibition of cell proliferation. As PADI2 is overexpressed in several cancers and is related to poor prognosis, selective inhibitors may help to prevent cancer progression.Peptidyl arginine deiminase 2 (PADI2) deiminates arginine (R1810) present at C-terminal domain of RNA polymerase II (RNAP2-CTD).PADI2 and R1810 of RNAP2-CTD regulate transcription of breast cancer cells.PADI2 depletion and absence of R1810 deimination at RNAP2-CTD inhibits proliferation of breast cancer cells.PADI2 mediated deimination of R1810 at RNAP2-CTD favors pause release. ER -