PMID- 14585982 OWN - NLM STAT- MEDLINE DCOM- 20031210 LR - 20210526 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 23 IP - 22 DP - 2003 Nov TI - The 5' untranslated region and Gag product of Idefix, a long terminal repeat-retrotransposon from Drosophila melanogaster, act together to initiate a switch between translated and untranslated states of the genomic mRNA. PG - 8246-54 AB - Idefix is a long terminal repeat (LTR)-retrotransposon present in Drosophila melanogaster which shares similarities with vertebrates retroviruses both in its genomic arrangement and in the mechanism of transposition. Like in retroviruses, its two LTRs flank a long 5' untranslated region (5'UTR) and three open reading frames referred to as the gag, pol, and env genes. Here we report that its 5'UTR, located upstream of the gag gene, can fold into highly structured domains that are known to be incompatible with efficient translation by ribosome scanning. Using dicistronic plasmids analyzed by both (i) in vitro transcription and translation in rabbit reticulocyte or wheat germ lysates and (ii) in vivo expression in transgenic flies, we show that the 5'UTR of Idefix exhibits an internal ribosome entry site (IRES) activity that is able to promote translation of a downstream cistron in a cap-independent manner. The functional state of this novel IRES depends on eukaryotic factors that are independent of their host origin. However, in vivo, its function can be down-regulated by trans-acting factors specific to tissues or developmental stages of its host. We identify one of these trans-acting factors as the Gag protein encoded by Idefix itself. Our data support a model in which nascent Gag is able to block translation initiated from the viral mRNA and thus its own translation. These data highlight the fact that LTR-retrotransposons may autoregulate their replication cycle through their Gag production. FAU - Meignin, Carine AU - Meignin C AD - Unite INSERM U384, Service de Bacteriologie-Virologie, Faculte de Medecine, 28 Place Henri Dunant, 63000 Clermont-Ferrand, France. FAU - Bailly, Jean-Luc AU - Bailly JL FAU - Arnaud, Frederick AU - Arnaud F FAU - Dastugue, Bernard AU - Dastugue B FAU - Vaury, Chantal AU - Vaury C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (5' Untranslated Regions) RN - 0 (RNA Caps) RN - 0 (RNA, Messenger) RN - 0 (Retroelements) SB - IM MH - 5' Untranslated Regions MH - Animals MH - Animals, Genetically Modified MH - Drosophila melanogaster/*genetics MH - Gene Silencing MH - Genes MH - Genes, Insect MH - Genes, gag MH - Lac Operon MH - Models, Genetic MH - Protein Biosynthesis MH - RNA Caps/genetics MH - RNA, Messenger/*genetics MH - Retroelements/*genetics MH - *Terminal Repeat Sequences PMC - PMC262410 EDAT- 2003/10/31 05:00 MHDA- 2003/12/12 05:00 PMCR- 2003/11/01 CRDT- 2003/10/31 05:00 PHST- 2003/10/31 05:00 [pubmed] PHST- 2003/12/12 05:00 [medline] PHST- 2003/10/31 05:00 [entrez] PHST- 2003/11/01 00:00 [pmc-release] AID - 0915 [pii] AID - 10.1128/MCB.23.22.8246-8254.2003 [doi] PST - ppublish SO - Mol Cell Biol. 2003 Nov;23(22):8246-54. doi: 10.1128/MCB.23.22.8246-8254.2003.