Symmetrical dimethylarginine methylation is required for the localization of SMN in Cajal bodies and pre-mRNA splicing

doi:10.1083/jcb.200207028

Published online 16 December 2002. doi:10.1083/jcb.200207028

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© The Rockefeller University Press, 0021-9525/2002/12/957 $5.00
The Journal of Cell Biology, Volume 159, Number 6, 957-969

Article

Symmetrical dimethylarginine methylation is required for the localization of SMN in Cajal bodies and pre-mRNA splicing

François-Michel Boisvert¹^,2, Jocelyn Côté¹^,2, Marie-Chloé Boulanger¹^,2, Patrick Cléroux¹^,2, François Bachand²^,3, Chantal Autexier²^,3 and Stéphane Richard¹^,2^,4

¹ Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montréal, Québec, Canada H3T 1E2
² Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montréal, Québec, Canada H3T 1E2
³ Department of Anatomy and Cell Biology, Medicine, Microbiology, and Immunology, McGill University, Montréal, Québec, Canada H3T 1E2
⁴ Departments of Oncology, Medicine, Microbiology, and Immunology, McGill University, Montréal, Québec, Canada H3T 1E2

Address correspondence to Stéphane Richard, Lady Davis Institute, 3755 Côte Ste-Catherine Rd., Montréal, Québec, Canada H3T 1E2. Tel.: (514) 340-8260. Fax: (514) 340-8295. E-mail: stephane.richard{at}mcgill.ca

The nuclear structures that contain symmetrical dimethylatedarginine (sDMA)–modified proteins and the role of thisposttranslational modification is unknown. Here we report thatthe Cajal body is a major epitope in HeLa cells for an sDMA-specificantibody and that coilin is an sDMA-containing protein as analyzedby using the sDMA-specific antibody and matrix-assisted laserdesorption ionization time of flight mass spectrometry. Themethylation inhibitor 5'-deoxy-5'-methylthioadenosine reducesthe levels of coilin methylation and causes the appearance ofSMN-positive gems. In cells devoid of Cajal bodies, such asprimary fibroblasts, sDMA-containing proteins concentrated inspeckles. Cells from a patient with spinal muscular atrophy,containing low levels of the methyl-binding protein SMN, localizedsDMA-containing proteins in the nucleoplasm as a discrete granularpattern. Splicing reactions are efficiently inhibited by usingthe sDMA-specific antibody or by using hypomethylated nuclearextracts, showing that active spliceosomes contain sDMA polypeptidesand suggesting that arginine methylation is important for efficientpre-mRNA splicing. Our findings support a model in which argininemethylation is important for the localization of coilin andSMN in Cajal bodies.

Key Words: PRMT5; Cajal; SMN; arginine methylation; splicing

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