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

Nature. 2016 Jan 7;529(7584):48-53. doi: 10.1038/nature16469. Epub 2015 Dec 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / metabolism*
  • Cell Line
  • DNA Damage
  • DNA Helicases
  • Humans
  • Methylation
  • Multifunctional Enzymes
  • Neurodegenerative Diseases / genetics
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / metabolism
  • RNA Helicases / genetics
  • RNA Helicases / metabolism
  • RNA Polymerase II / chemistry*
  • RNA Polymerase II / metabolism*
  • Survival of Motor Neuron 1 Protein / genetics
  • Survival of Motor Neuron 1 Protein / metabolism*
  • Transcription Elongation, Genetic
  • Transcription Termination, Genetic*


  • Multifunctional Enzymes
  • SMN1 protein, human
  • Survival of Motor Neuron 1 Protein
  • Arginine
  • PRMT5 protein, human
  • Protein-Arginine N-Methyltransferases
  • RNA Polymerase II
  • SETX protein, human
  • DNA Helicases
  • RNA Helicases

Associated data

  • GEO/GSE73379