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J. Biol. Chem., Vol. 278, Issue 16, 14168-14173, April 18, 2003

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mRNA Capping Enzyme Requirement for Caenorhabditis elegans Viability^*

Priya Srinivasan^§, Fabio Piano^¶, and Aaron J. Shatkin^§

From the  Center for Advanced Biotechnology and Medicine and ^§ Graduate Program in Biochemistry, Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854 and ^¶ Department of Biology, New York University, New York, New York 10012

Capping of the initiated 5' ends of RNA polymerase II products is evolutionarily and functionally conserved from yeasts to humans. The m⁷GpppN cap promotes RNA stability, processing, transport, and translation. Deletion of capping enzymes in yeasts was shown to be lethal due to rapid exonucleolytic degradation of uncapped transcripts or failure of capped but unmethylated RNA to initiate protein synthesis. Using RNA interference and Caenorhabditis elegans we have found that RNA capping is also essential for metazoan viability. C. elegans bifunctional capping enzyme was cloned, and capping activity by the expressed protein as well as growth complementation of yeast deletion strains missing either RNA triphosphatase or guanylyltransferase required terminal sequences not present in the previously isolated cel-1 clone. By RNA interference analysis we show that cel-1 is required for embryogenesis. cel-1(RNAi) embryos formed cytoplasmic granules characteristic of a phenocluster of RNA processing genes and died early in development.

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