Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Department of Embryology, Carnegie Institution, 3520 San Martin Drive, Baltimore, MD 21218, USA; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Cell. 2014 Feb 13;156(4):800-11. doi: 10.1016/j.cell.2014.01.021.
Bacterial and viral mRNAs are often polycistronic. Akin to alternative splicing, alternative translation of polycistronic messages is a mechanism to generate protein diversity and regulate gene function. Although a few examples exist, the use of polycistronic messages in mammalian cells is not widely appreciated. Here we report an example of alternative translation as a means of regulating innate immune signaling. MAVS, a regulator of antiviral innate immunity, is expressed from a bicistronic mRNA encoding a second protein, miniMAVS. This truncated variant interferes with interferon production induced by full-length MAVS, whereas both proteins positively regulate cell death. To identify other polycistronic messages, we carried out genome-wide ribosomal profiling and identified a class of antiviral truncated variants. This study therefore reveals the existence of a functionally important bicistronic antiviral mRNA and suggests a widespread role for polycistronic mRNAs in the innate immune system.
细菌和病毒的 mRNA 通常是多顺反子的。类似于选择性剪接，多顺反子mRNA 的选择性翻译是产生蛋白质多样性和调节基因功能的一种机制。尽管存在少数几个例子，但多顺反子mRNA 在哺乳动物细胞中的应用尚未得到广泛认识。在这里，我们报告了一种作为调节先天免疫信号的选择性翻译的例子。MAVS 是抗病毒先天免疫的调节剂，由编码第二个蛋白 miniMAVS 的双顺反子 mRNA 表达。这种截断的变体干扰由全长 MAVS 诱导的干扰素产生，而这两种蛋白都正向调节细胞死亡。为了鉴定其他多顺反子 mRNA，我们进行了全基因组核糖体谱分析，并鉴定出一类抗病毒截断变体。因此，本研究揭示了一种具有重要功能的双顺反子抗病毒 mRNA 的存在，并表明多顺反子 mRNA 在先天免疫系统中具有广泛的作用。
