Unconventional translation of mammalian LINE-1 retrotransposons.
Long Interspersed Element-1 (LINE-1 or L1) retrotransposons encode proteins required for their mobility (ORF1p and ORF2p), yet little is known about how L1 mRNA is translated. Here, we show that ORF2 translation generally initiates from the first in-frame methionine codon of ORF2, and that both ORF1 and the inter-ORF spacer are dispensable for ORF2 translation. Remarkably, changing the ORF2 AUG codon to any other coding triplet is compatible with retrotransposition. However, introducing a premature termination codon in ORF1 or a thermostable hairpin in the inter-ORF spacer reduces ORF2p translation or L1 retrotransposition to approximately 5% of wild-type levels. Similar data obtained from "natural" and codon optimized "synthetic" mouse L1s lead us to propose that ORF2 is translated by an unconventional termination/reinitiation mechanism.
Alisch
Reid S
RS
Department of Human Genetics and Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0618, USA.
Garcia-Perez
Jose L
JL
Muotri
Alysson R
AR
Gage
Fred H
FH
Moran
John V
JV
D000818:Animals; D001483:Base Sequence; D018387:Codon, Initiator / Q000235:genetics; D018388:Codon, Terminator / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D010442:Peptide Chain Initiation, Translational / Q000235:genetics*; D018626:Retroelements / Q000235:genetics* / Q000502:physiology
D018387:Codon, Initiator; D018388:Codon, Terminator; D018626:Retroelements