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...

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Bibliographic Details
Published in:Genes & development 2006-01, Vol.20 (2), p.210-224
Main Authors: Alisch, Reid S, Garcia-Perez, Jose L, Muotri, Alysson R, Gage, Fred H, Moran, John V
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Codon, Initiator - genetics
Codon, Terminator - genetics
HeLa Cells
Humans
Long Interspersed Nucleotide Elements - genetics
Long Interspersed Nucleotide Elements - physiology
Mice
Models, Genetic
Molecular Sequence Data
Open Reading Frames - genetics
Peptide Chain Initiation, Translational - genetics
Research Papers
Retroelements - genetics
Retroelements - physiology
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Description
Summary: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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.1380406