Sharma, P.* ; Lioutas, A.* ; Fernandez-Fuentes, N.* ; Quilez, J.* ; Carbonell-Caballero, J.* ; Wright, R.H.G.* ; Di Vona, C.* ; Le Dily, F.* ; Schüller, R. ; Eick, D. ; Oliva, B.* ; Beato, M.*
Arginine citrullination at the C-terminal domain controls RNA polymerase II transcription.
Mol. Cell 73, 84-96 (2018)
The post-translational modification of key residues at the C-terminal domain of RNA polymerase II (RNAP2-CTD) coordinates transcription, splicing, and RNA processing by modulating its capacity to act as a landing platform for a variety of protein complexes. Here, we identify a new modification at the CTD, the deimination of arginine and its conversion to citrulline by peptidyl arginine deiminase 2 (PADI2), an enzyme that has been associated with several diseases, including cancer. We show that, among PADI family members, only PADI2 citrullinates R1810 (Cit1810) at repeat 31 of the CTD. Depletion of PADI2 or loss of R1810 results in accumulation of RNAP2 at transcription start sites, reduced gene expression, and inhibition of cell proliferation. Cit1810 is needed for interaction with the P-TEFb (positive transcription elongation factor b) kinase complex and for its recruitment to chromatin. In this way, CTD-Cit1810 favors RNAP2 pause release and efficient transcription in breast cancer cells.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Arginine1810 ; Breast Cancer Cells ; Cell Proliferation ; Citrullination ; P-tefb Complex ; Padi2 ; Proximal Promoter Pausing ; Rna Polymerase Ii Ctd; Multiple Sequence Alignment; Microarray Data; Protein; Expression; Ctd; Genes; Methylation; Elongation; Nucleosome; Reveals
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2018
Prepublished im Jahr
HGF-Berichtsjahr
2018
ISSN (print) / ISBN
1097-2765
e-ISSN
1097-4164
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 73,
Heft: 1,
Seiten: 84-96
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Elsevier
Verlagsort
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Tag d. mündl. Prüfung
0000-00-00
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Prüfer
Topic
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Veröffentlichungsdatum
0000-00-00
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0000-00-00
Anmelder/Inhaber
weitere Inhaber
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Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30203 - Molecular Targets and Therapies
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-502890-001
Förderungen
Copyright
Erfassungsdatum
2018-12-07