Eckwahl Matthew J, Sim Soyeong, Smith Derek, Telesnitsky Alice, Wolin Sandra L
Department of Cell Biology, Yale School of Medicine, New Haven, Connecticut 06536, USA.
Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, Connecticut 06536, USA.
Genes Dev. 2015 Mar 15;29(6):646-57. doi: 10.1101/gad.258731.115.
Although all retroviruses recruit host cell RNAs into virions, both the spectrum of RNAs encapsidated and the mechanisms by which they are recruited remain largely unknown. Here, we used high-throughput sequencing to obtain a comprehensive description of the RNAs packaged by a model retrovirus, murine leukemia virus. The major encapsidated host RNAs are noncoding RNAs (ncRNAs) and members of the VL30 class of endogenous retroviruses. Remarkably, although Moloney leukemia virus (MLV) assembles in the cytoplasm, precursors to specific tRNAs, small nuclear RNAs (snRNAs), and small nucleolar RNAs (snoRNAs) are all enriched in virions. Consistent with their cytoplasmic recruitment, packaging of both pre-tRNAs and U6 snRNA requires the nuclear export receptor Exportin-5. Adenylated and uridylated forms of these RNAs accumulate in cells and virions when the cytoplasmic exoribonuclease DIS3L2 and subunits of the RNA exosome are depleted. Together, our data reveal that MLV recruits RNAs from a novel host cell surveillance pathway in which unprocessed and unneeded nuclear ncRNAs are exported to the cytoplasm for degradation.
尽管所有逆转录病毒都会将宿主细胞RNA纳入病毒粒子，但被包裹的RNA种类及其纳入机制在很大程度上仍不清楚。在此，我们利用高通量测序对一种模型逆转录病毒——鼠白血病病毒所包裹的RNA进行了全面描述。主要被包裹的宿主RNA是非编码RNA（ncRNA）以及内源性逆转录病毒VL30类的成员。值得注意的是，尽管莫洛尼白血病病毒（MLV）在细胞质中组装，但特定tRNA的前体、小核RNA（snRNA）和小核仁RNA（snoRNA）在病毒粒子中均有富集。与它们在细胞质中的纳入情况一致，前体tRNA和U6 snRNA的包裹都需要核输出受体Exportin-5。当细胞质外切核糖核酸酶DIS3L2和RNA外切体的亚基缺失时，这些RNA的腺苷酸化和尿苷酸化形式会在细胞和病毒粒子中积累。总之，我们的数据表明，MLV从一种新的宿主细胞监测途径中获取RNA，在该途径中，未加工且不需要的核ncRNA被输出到细胞质中进行降解。
