Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60:543-548 (2005)
© 2005 The Gerontological Society of America

Functional Analysis of MRG-1: The Ortholog of Human MRG15 in Caenorhabditis elegans

Abdullah Olgun1, Tetyana Aleksenko2, Olivia M. Pereira-Smith3 and Demetrios K. Vassilatis4

1 Roy M. and Phyllis Gough Huffington Center on Aging, Baylor College of Medicine, Houston, Texas.
2 Tetyana Aleksenko is now with the Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030-3498.
3 Olivia M. Pereira-Smith is now with the Department of Cellular and Structural Biology, Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, STCBM, 15355 Lambda Drive, San Antonio, Texas 78245-3207.
4 Demetrios K. Vassilatis is now with the Foundation for Biomedical Research of the Academy of Athens, Soranou Efessiou 4, 115 27 Athens, Greece.

Address correspondence to Abdullah Olgun, MD, Department of Biochemistry and Clinical Biochemistry, Gülhane School of Medicine, Etlik-06018, Ankara, Turkey. E-mail: aolgun{at}yahoo.com

Mortality Factor on Chromosome 4 (MORF4) induces senescence in several immortal human cell lines. MORF-related gene on chromosome 15 (MRG15), another expressed family member, is highly conserved and expressed in yeast to humans. To determine the biological functions of human MRG15 (hMRG15) we used RNA-mediated interference (RNAi) to silence mrg-1, the Caenorhabditis elegans ortholog, and its closest homolog Y37D8A.11. Expression of mrg-1 RNAi resulted in sterility, body wall defects, vulval protrusion, and posterior developmental defects in worms. We expressed mrg-1 under its own and the cytomegalovirus promoter in human cells. Both constructs were expressed, indicating that C. elegans promoter elements are functional in mammalian cells. Overexpression from the cytomegalovirus promoter eventually resulted in cell death, possibly due to competition with hMRG15 in endogenous nucleoprotein complexes. Recent data indicate a role for yeast and human MRG15 in transcriptional regulation via chromatin remodeling. Here we demonstrate the importance of mrg-1 in development and reproduction in C. elegans and discuss its potential to impact the aging process.






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