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

Abstract:

: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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Manktelow E,Shigemoto K,Brierley I

doi

10.1093/nar/gki299

keywords:

subject

Has Abstract

pub_date

2005-03-14 00:00:00

pages

1553-63

issue

5

eissn

0305-1048

issn

1362-4962

pii

33/5/1553

journal_volume

33

pub_type

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