Identification and characterisation of a developmentally regulated mammalian gene that utilises -1 programmed ribosomal frameshifting.
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.
Shigemoto
K
K
Ludwig Institute for Cancer Research, 91 Riding House Street, London W1P 8BT, UK. shigemoto@m.ehime-u.ac.jp
Brennan
J
J
Walls
E
E
Watson
C J
CJ
Stott
D
D
Rigby
P W
PW
Reith
A D
AD
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D002874:Chromosome Mapping; D017124:Conserved Sequence; D018965:Frameshifting, Ribosomal; D018507:Gene Expression Regulation, Developmental; D016679:Genome, Viral; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000196:embryology; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012190:Retroviridae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D016335:Zinc Fingers
D002352:Carrier Proteins; C437720:Edr protein, mouse; D010455:Peptides; D012333:RNA, Messenger; D016282:Aspartic Acid Endopeptidases