Uncoupling the pleiotropic phenotypes of clk-1 with tRNA missense suppressors in Caenorhabditis elegans.

Molecular and Cellular Biology
Robyn BranickySiegfried Hekimi

Abstract

clk-1 encodes a demethoxyubiquinone (DMQ) hydroxylase that is necessary for ubiquinone biosynthesis. When Caenorhabditis elegans clk-1 mutants are grown on bacteria that synthesize ubiquinone (UQ), they are viable but have a pleiotropic phenotype that includes slowed development, behaviors, and aging. However, when grown on UQ-deficient bacteria, the mutants arrest development transiently before growing up to become sterile adults. We identified nine suppressors of the missense mutation clk-1(e2519), which harbors a Glu-to-Lys substitution. All suppress the mutant phenotypes on both UQ-replete and UQ-deficient bacteria. However, each mutant suppresses a different subset of phenotypes, indicating that most phenotypes can be uncoupled from each other. In addition, all suppressors restore the ability to synthesize exceedingly small amounts of UQ, although they still accumulate the precursor DMQ, suggesting that the presence of DMQ is not responsible for the Clk-1 phenotypes. We cloned six of the suppressors, and all encode tRNA(Glu) genes whose anticodons are altered to read the substituted Lys codon of clk-1(e2519). To our knowledge, these suppressors represent the first missense suppressors identified in any metazoan. The patter...Continue Reading

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Citations

Mar 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Manish RauthanMarc Pilon
May 30, 2009·The Journal of Biological Chemistry·Jérôme LapointeSiegfried Hekimi
Jul 19, 2008·The Journal of Biological Chemistry·Jérôme Lapointe, Siegfried Hekimi
Oct 3, 2012·Antioxidants & Redox Signaling·Daniel A PulliamHolly Van Remmen
Nov 30, 2012·Critical Reviews in Biochemistry and Molecular Biology·Ying Wang, Siegfried Hekimi
Jul 13, 2011·Mechanisms of Ageing and Development·Yu-Ying YangPhil G Morgan
Aug 8, 2006·Experimental Gerontology·Zaruhi StepanyanSiegfried Hekimi
Apr 15, 2017·Journal of Cellular and Molecular Medicine·Ying WangSiegfried Hekimi
Oct 18, 2008·The Journal of Biological Chemistry·Ying WangSiegfried Hekimi
Apr 14, 2017·Scientific Reports·Ju-Ling LiuSiegfried Hekimi

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