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SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination

Author

Listed:
  • Dorothy Yanling Zhao

    (Donnelly Centre, University of Toronto
    Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue
    University of Toronto)

  • Gerald Gish

    (Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue)

  • Ulrich Braunschweig

    (Donnelly Centre, University of Toronto)

  • Yue Li

    (Donnelly Centre, University of Toronto
    University of Toronto)

  • Zuyao Ni

    (Donnelly Centre, University of Toronto)

  • Frank W. Schmitges

    (Donnelly Centre, University of Toronto)

  • Guoqing Zhong

    (Donnelly Centre, University of Toronto)

  • Ke Liu

    (Structural Genomics Consortium, University of Toronto)

  • Weiguo Li

    (Structural Genomics Consortium, University of Toronto)

  • Jason Moffat

    (Donnelly Centre, University of Toronto
    University of Toronto)

  • Masoud Vedadi

    (Structural Genomics Consortium, University of Toronto)

  • Jinrong Min

    (Structural Genomics Consortium, University of Toronto)

  • Tony J. Pawson

    (Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue
    University of Toronto)

  • Benjamin J. Blencowe

    (Donnelly Centre, University of Toronto
    University of Toronto)

  • Jack F. Greenblatt

    (Donnelly Centre, University of Toronto
    University of Toronto)

Abstract

The carboxy-terminal domain (CTD) of the RNA polymerase II (RNAP II) subunit POLR2A is a platform for modifications specifying the recruitment of factors that regulate transcription, mRNA processing, and chromatin remodelling. Here we show that a CTD arginine residue (R1810 in human) that is conserved across vertebrates is symmetrically dimethylated (me2s). This R1810me2s modification requires protein arginine methyltransferase 5 (PRMT5) and recruits the Tudor domain of the survival of motor neuron (SMN, also known as GEMIN1) protein, which is mutated in spinal muscular atrophy. SMN interacts with senataxin, which is sometimes mutated in ataxia oculomotor apraxia type 2 and amyotrophic lateral sclerosis. Because POLR2A R1810me2s and SMN, like senataxin, are required for resolving RNA–DNA hybrids created by RNA polymerase II that form R-loops in transcription termination regions, we propose that R1810me2s, SMN, and senataxin are components of an R-loop resolution pathway. Defects in this pathway can influence transcription termination and may contribute to neurodegenerative disorders.

Suggested Citation

  • Dorothy Yanling Zhao & Gerald Gish & Ulrich Braunschweig & Yue Li & Zuyao Ni & Frank W. Schmitges & Guoqing Zhong & Ke Liu & Weiguo Li & Jason Moffat & Masoud Vedadi & Jinrong Min & Tony J. Pawson & B, 2016. "SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination," Nature, Nature, vol. 529(7584), pages 48-53, January.
    • Handle: RePEc:nat:nature:v:529:y:2016:i:7584:d:10.1038_nature16469
    DOI: 10.1038/nature16469
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    Cited by:

    1. Hidehiro Itonaga & Adnan K. Mookhtiar & Sarah M. Greenblatt & Fan Liu & Concepcion Martinez & Daniel Bilbao & Masai Rains & Pierre-Jacques Hamard & Jun Sun & Afoma C. Umeano & Stephanie Duffort & Chua, 2024. "Tyrosine phosphorylation of CARM1 promotes its enzymatic activity and alters its target specificity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Yanli Liu & Aman Iqbal & Weiguo Li & Zuyao Ni & Yalong Wang & Jurupula Ramprasad & Karan Joshua Abraham & Mengmeng Zhang & Dorothy Yanling Zhao & Su Qin & Peter Loppnau & Honglv Jiang & Xinghua Guo & , 2022. "A small molecule antagonist of SMN disrupts the interaction between SMN and RNAP II," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Anja Deutzmann & Delaney K. Sullivan & Renumathy Dhanasekaran & Wei Li & Xinyu Chen & Ling Tong & Wadie D. Mahauad-Fernandez & John Bell & Adriane Mosley & Angela N. Koehler & Yulin Li & Dean W. Felsh, 2024. "Nuclear to cytoplasmic transport is a druggable dependency in MYC-driven hepatocellular carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Shaqraa Musawi & Lise-Marie Donnio & Zehui Zhao & Charlène Magnani & Phoebe Rassinoux & Olivier Binda & Jianbo Huang & Arnaud Jacquier & Laurent Coudert & Patrick Lomonte & Cécile Martinat & Laurent S, 2023. "Nucleolar reorganization after cellular stress is orchestrated by SMN shuttling between nuclear compartments," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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