Functional analysis of MRG-1: the ortholog of human MRG15 in Caenorhabditis elegans.
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.
Olgun
Abdullah
A
Department of Biochemistry and Clinical Biochemistry, Gülhane School of Medicine, Etlik-06018, Ankara, Turkey. aolgun@yahoo.com
Aleksenko
Tetyana
T
Pereira-Smith
Olivia M
OM
Vassilatis
Demetrios K
DK
D000375:Aging / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology*; D016923:Cell Death / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells / Q000469:parasitology; D006801:Humans; D008136:Longevity / Q000502:physiology; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics*
D029742:Caenorhabditis elegans Proteins; C109882:MORF4 protein, human; C470833:MORF4L1 protein, human; C470832:MRG-1 protein, C elegans; D014157:Transcription Factors