Garcia-Moreno Manuel, Sanz Miguel Angel, Carrasco Luis
Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Madrid, Spain.
Sci Rep. 2016 Jan 12;6:19217. doi: 10.1038/srep19217.
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.
辛德毕斯病毒(SINV)的信使核糖核酸(mRNA)包含几个参与其翻译调控的基序。我们在病毒mRNA的3'非翻译区(UTR)发现了一个由三个重复序列构成的基序,它参与了SINV基因组和亚基因组mRNA在昆虫细胞而非哺乳动物细胞中的翻译。这些数据首次表明,位于3'-UTR的一个元件以细胞特异性方式赋予动物病毒mRNA可翻译性。位于5'-UTR起始处的序列在感染情况下也可能调节两种细胞系中SINV亚基因组mRNA的翻译。此外,当将来自SINV的重复序列插入其3'-UTR时,源自昏睡病病毒(一种没有已知节肢动物传播载体的甲病毒)的复制子在昆虫细胞中的效率要高得多,这是因为其mRNA的可翻译性增强。因此,这些发现为从分子水平理解甲病毒的进化及其宿主范围提供了线索。