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Nucleic Acids Research 2005 33(5):1553-1563; doi:10.1093/nar/gki299
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Published online 14 March 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org

Article

Characterization of the frameshift signal of Edr, a mammalian example of programmed –1 ribosomal frameshifting

Emily Manktelow, Kazuhiro Shigemoto1 and Ian Brierley*

Division of Virology, Department of Pathology University of Cambridge Tennis Court Road, Cambridge CB2 1QP, UK 1Department of Environmental Health and Social Medicine, Ehime University School of Medicine Shitsukawa, Toon, Ehime 791-0295 Japan

*To whom correspondence should be addressed. Tel: +44 1223 336914; Fax: +44 1223 336926; Email: ib103{at}mole.bio.cam.ac.uk

Received January 26, 2005. Revised February 23, 2005. Accepted February 23, 2005.

The ribosomal frameshifting signal of the mouse embryonal carcinoma differentiation regulated (Edr) gene represents the sole documented example of programmed –1 frameshifting in mammalian cellular genes [Shigemoto,K., Brennan,J., Walls,E,. Watson,C.J., Stott,D., Rigby,P.W. and Reith,A.D. (2001), Nucleic Acids Res., 29, 4079–4088]. Here, we have employed site-directed mutagenesis and RNA structure probing to characterize the Edr signal. We began by confirming the functionality and magnitude of the signal and the role of a GGGAAAC motif as the slippery sequence. Subsequently, we derived a model of the Edr stimulatory RNA and assessed its similarity to those stimulatory RNAs found at viral frameshift sites. We found that the structure is an RNA pseudoknot possessing features typical of retroviral frameshifter pseudoknots. From these experiments, we conclude that the Edr signal and by inference, the human orthologue PEG10, do not represent a novel ‘cellular class’ of programmed –1 ribosomal frameshift signal, but rather are similar to viral examples, albeit with some interesting features. The similarity to viral frameshift signals may complicate the design of antiviral therapies that target the frameshift process.


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