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New Directions for Understanding the Codon Redefinition Required for Selenocysteine Incorporation

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Abstract

The fact that selenocysteine (Sec) is delivered to the elongating ribosome by a tRNA that recognizes a UGA stop codon makes it unique and a thorn in the side of what was originally thought to be a universal genetic code. The mechanism by which this redefinition occurs has been slowly coming to light over the past 30 years, but key questions remain. This review seeks to highlight the prominent mechanistic questions that will guide the direction of work in the near future. These questions arise from two major aspects of Sec incorporation: (1) novel functions for the Sec insertion sequence (SECIS) that resides in all selenoprotein mRNAs and (2) the myriad of RNA-binding proteins, both known and yet to be discovered, that act in concert to modify the translation elongation process to allow Sec incorporation.

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Acknowledgments

This work was supported by National Institutes of Health grants GM077073 (PRC) and GM114291 (MTH).

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  1. Department of Human Genetics, University of Utah, Salt Lake City, UT, USA

    Michael T. Howard

  2. Department of Biochemistry and Molecular Biology, Rutgers Robert Wood Johnson Medical School, 675 Hoes Ln, Piscataway, NJ, 08854, USA

    Paul R. Copeland

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Howard, M.T., Copeland, P.R. New Directions for Understanding the Codon Redefinition Required for Selenocysteine Incorporation. Biol Trace Elem Res 192, 18–25 (2019). https://doi.org/10.1007/s12011-019-01827-y

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