Abstract
Sindbis virus (SINV) mRNAs contain several motifs that participate in the regulation of their translation. We have discovered a motif at the 3′ untranslated region (UTR) of viral mRNAs, constituted by three repeated sequences, which is involved in the translation of both SINV genomic and subgenomic mRNAs in insect, but not in mammalian cells. These data illustrate for the first time that an element present at the 3′-UTR confers translatability to mRNAs from an animal virus in a cell-specific manner. Sequences located at the beginning of the 5′-UTR may also regulate SINV subgenomic mRNA translation in both cell lines in a context of infection. Moreover, a replicon derived from Sleeping disease virus, an alphavirus that have no known arthropod vector for transmission, is much more efficient in insect cells when the repeated sequences from SINV are inserted at its 3′-UTR, due to the enhanced translatability of its mRNAs. Thus, these findings provide a clue to understand, at the molecular level, the evolution of alphaviruses and their host range.
Highlights
Translation Element) and can be found in different regions of the genome, they are most frequently located at the 3′ -untranslated region (UTR)
Translation of the sgmRNA derived from this replicon produces a fusion protein that is cleaved at the C carboxyl-terminus immediately after its generation due to the autocatalytic activity of C, releasing C and luciferase proteins
Mutation of the 3′ -UTR of Sindbis virus (SINV) rep has little effect on the synthesis of proteins directed by g- and sgmRNA in mammalian cells
Summary
Translation Element) and can be found in different regions of the genome, they are most frequently located at the 3′ -UTR. CITEs have not yet been described in RNA genomes from animal viruses In addition to these elements, long-range interactions between the 5′ and 3′ regions of RNA from positive-stranded viruses have been shown to be involved in RNA replication, transcription or translation[8]. EIF4E, a component of the eIF4F complex, binds to the cap structure present at the 5′ end of mRNAs, whereas poly(A) binding protein (PABP) interacts with the poly(A) tail that is located at the 3′ end. A number of elements have been distinguished in sgmRNA that make it efficient for translation during infection Among these is the hairpin-loop structure, known as DLP, located 24 nucleotides downstream of the AUG initiation codon that is required to translate the sgmRNA in the absence of active eIF2 in SINV-infected mammalian cells[18,19,20]. The leader sequence of sgmRNA has been shown to be involved in the translatability of sgmRNA and in the shut-off of host translation[22]
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