This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Mitchell, T. R. H.
Right arrow Articles by Zhu, X.-D.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mitchell, T. R. H.
Right arrow Articles by Zhu, X.-D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2009, p. 4918-4934, Vol. 29, No. 18
0270-7306/09/$08.00+0     doi:10.1128/MCB.00009-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Arginine Methylation Regulates Telomere Length and Stability{triangledown}

Taylor R. H. Mitchell, Kimberly Glenfield, Kajaparan Jeyanthan, and Xu-Dong Zhu*

Department of Biology, McMaster University, Hamilton, Ontario, Canada L8S 4K1

Received 4 January 2009/ Returned for modification 26 February 2009/ Accepted 22 June 2009

TRF2, a component of the shelterin complex, functions to protect telomeres. TRF2 contains an N-terminal basic domain rich in glycines and arginines, similar to the GAR motif that is methylated by protein arginine methyltransferases. However, whether arginine methylation regulates TRF2 function has not been determined. Here we report that amino acid substitutions of arginines with lysines in the basic domain of TRF2 induce telomere dysfunction-induced focus formation, leading to induction of cellular senescence. We have demonstrated that cells overexpressing TRF2 lysine mutants accumulate telomere doublets, indicative of telomere instability. We uncovered that TRF2 interacts with PRMT1, and its arginines in the basic domain undergo PRMT1-mediated methylation both in vitro and in vivo. We have shown that loss of PRMT1 induces growth arrest in normal human cells but has no effect on cell proliferation in cancer cells, suggesting that PRMT1 may control cell proliferation in a cell type-specific manner. We found that depletion of PRMT1 in normal human cells results in accumulation of telomere doublets, indistinguishable from overexpression of TRF2 lysine mutants. PRMT1 knockdown in cancer cells upregulates TRF2 association with telomeres, promoting telomere shortening. Taken together, these results suggest that PRMT1 may control telomere length and stability in part through TRF2 methylation.

* Corresponding author. Mailing address: Department of Biology, LSB438, McMaster University, 1280 Main St. West, Hamilton, Ontario, Canada L8S 4K1. Phone: (905) 525-9140, ext. 27737. Fax: (905) 522-6066. E-mail: zhuxu{at}mcmaster.ca

{triangledown} Published ahead of print on 13 July 2009.

Molecular and Cellular Biology, September 2009, p. 4918-4934, Vol. 29, No. 18
0270-7306/09/$08.00+0     doi:10.1128/MCB.00009-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»