title: The C-terminal domain of RNA polymerase II is modified by site-specific methylation.
abstract: The carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII) in mammals undergoes extensive posttranslational modification, which is essential for transcriptional initiation and elongation. Here, we show that the CTD of RNAPII is methylated at a single arginine (R1810) by the coactivator-associated arginine methyltransferase 1 (CARM1). Although methylation at R1810 is present on the hyperphosphorylated form of RNAPII in vivo, Ser2 or Ser5 phosphorylation inhibits CARM1 activity toward this site in vitro, suggesting that methylation occurs before transcription initiation. Mutation of R1810 results in the misexpression of a variety of small nuclear RNAs and small nucleolar RNAs, an effect that is also observed in Carm1(-/-) mouse embryo fibroblasts. These results demonstrate that CTD methylation facilitates the expression of select RNAs, perhaps serving to discriminate the RNAPII-associated machinery recruited to distinct gene types.
authors: Howard Hughes Medical Institute (HHMI), Department of Biochemistry, New York University School of Medicine, 522 First Avenue, Smilow 211, New York, NY 10016, USA.
authors: Robert J
authors: RJ
authors: Sims
authors: Howard Hughes Medical Institute (HHMI), Department of Biochemistry, New York University School of Medicine, 522 First Avenue, Smilow 211, New York, NY 10016, USA.
authors: Luis Alejandro
authors: LA
authors: Rojas
authors: Howard Hughes Medical Institute (HHMI), Department of Biochemistry, New York University School of Medicine, 522 First Avenue, Smilow 211, New York, NY 10016, USA.
authors: David B
authors: DB
authors: Beck
authors: Howard Hughes Medical Institute (HHMI), Department of Biochemistry, New York University School of Medicine, 522 First Avenue, Smilow 211, New York, NY 10016, USA.
authors: Roberto
authors: R
authors: Bonasio
authors: Department of Molecular Epigenetics, Helmholtz Center Munich, Center of Integrated Protein Science Munich (CIPSM), Marchioninistrasse 25, 81377 Munich, Germany.
authors: Roland
authors: R
authors: Schüller
authors: Howard Hughes Medical Institute (HHMI), Department of Biochemistry, New York University School of Medicine, 522 First Avenue, Smilow 211, New York, NY 10016, USA.
authors: William J
authors: WJ
authors: Drury
authors: Department of Molecular Epigenetics, Helmholtz Center Munich, Center of Integrated Protein Science Munich (CIPSM), Marchioninistrasse 25, 81377 Munich, Germany.
authors: Dirk
authors: D
authors: Eick
authors: Howard Hughes Medical Institute (HHMI), Department of Biochemistry, New York University School of Medicine, 522 First Avenue, Smilow 211, New York, NY 10016, USA.
authors: Danny
authors: D
authors: Reinberg
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D051379:Mice; D009154:Mutation; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012342:RNA, Small Nuclear / Q000378:metabolism; D020537:RNA, Small Nucleolar / Q000378:metabolism; D011994:Recombinant Proteins
chemical_list: D012342:RNA, Small Nuclear; D020537:RNA, Small Nucleolar; D011994:Recombinant Proteins; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1; D012319:RNA Polymerase II