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Nucleic Acids Research, 2001, Vol. 29, No. 19 4079-4088
© 2001 Oxford University Press

Identification and characterisation of a developmentally regulated mammalian gene that utilises –1 programmed ribosomal frameshifting

Kazuhiro Shigemoto1, Jane Brennan1, Elizabeth Walls1, Christine J. Watson2, David Stott3, Peter W. J. Rigby2,3 and Alastair D. Reith1,2,3,*

1Ludwig Institute for Cancer Research, 91 Riding House Street, London W1P 8BT, UK, 2CRC Eukaryotic Molecular Genetic Research Group, Department of Biochemistry, Imperial College of Science and Technology, London SW7 2AZ, UK and 3Division of Eukaryotic Molecular Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, NW7 1AA, UK

Translational recoding of mRNA through a –1 ribosomal slippage mechanism has been observed in RNA viruses and retrotransposons of both eukaryotes and prokaryotes. Whilst this provides a potentially powerful mechanism of gene regulation, the utilization of –1 translational frameshifting in regulating mammalian gene expression has remained obscure. Here we report a mammalian gene, Edr, which provides the first example of –1 translational recoding in a eukaryotic cellular gene. In addition to bearing functional frameshift elements that mediate expression of distinct polypeptides, Edr bears both CCHC zinc-finger and putative aspartyl protease catalytic site retroviral-like motifs, indicative of a relic retroviral-like origin for Edr. These features, coupled with conservation of Edr as a single copy gene in mouse and man and striking spatio-temporal regulation of expression during embryogenesis, suggest that Edr plays a functionally important role in mammalian development.

* To whom correspondence should be addressed at: Systems Research, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park North, Third Avenue, Harlow CM19 5AW, UK. Tel: +44 1279 62 2288; Fax: +44 1279 62 2371; Email: alastair_d_reith{at}gsk.com Correspondence may also be addressed to Kazuhiro Shigemoto at present address: Department of Hygiene, School of Medicine, Ehime University, Ehime, 791-0295, Japan. Tel: +81 89 960 5278; Fax: +81 89 960 5279; Email: shigemoto{at}m.ehime-u.ac.jpPresent addresses:Jane Brennan, Department Molecular and Cellular Biology, Harvard University, Divinity Avenue Cambridge, MA 02138, USAChristine J. Watson, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UKDavid Stott, Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UKPeter W. J. Rigby, Section of Gene Function and Regulation, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK


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