Publication Date:
2015-12-25
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Dorothy Yanling -- Gish, Gerald -- Braunschweig, Ulrich -- Li, Yue -- Ni, Zuyao -- Schmitges, Frank W -- Zhong, Guoqing -- Liu, Ke -- Li, Weiguo -- Moffat, Jason -- Vedadi, Masoud -- Min, Jinrong -- Pawson, Tony J -- Blencowe, Benjamin J -- Greenblatt, Jack F -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2016 Jan 7;529(7584):48-53. doi: 10.1038/nature16469. Epub 2015 Dec 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. ; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada. ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Department of Computer Science, University of Toronto, Toronto, Ontario M5S 3G4, Canada. ; Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26700805" target="_blank"〉PubMed〈/a〉
Keywords:
Arginine/*metabolism
;
Cell Line
;
DNA Damage
;
Humans
;
Methylation
;
Neurodegenerative Diseases/genetics
;
Protein Binding
;
Protein Structure, Tertiary
;
Protein-Arginine N-Methyltransferases/genetics/metabolism
;
RNA Helicases/genetics/metabolism
;
RNA Polymerase II/*chemistry/*metabolism
;
Survival of Motor Neuron 1 Protein/genetics/*metabolism
;
Transcription Elongation, Genetic
;
*Transcription Termination, Genetic
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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