Characterization of the frameshift signal of Edr, a mammalian example of programmed -1 ribosomal frameshifting.
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.
Manktelow
Emily
E
Division of Virology, Department of Pathology University of Cambridge Tennis Court Road, Cambridge CB2 1QP, UK.
Shigemoto
Kazuhiro
K
Brierley
Ian
I
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins; D018965:Frameshifting, Ribosomal; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry*; D016601:RNA-Binding Proteins
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C437720:Edr protein, mouse; C432965:PEG10 protein, human; D011506:Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins