Spurlock Charles F, Shaginurova Guzel, Tossberg John T, Hester Jonathan D, Chapman Nathaniel, Guo Yan, Crooke Philip S, Aune Thomas M
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232.
Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.
J Immunol. 2017 Jul 15;199(2):547-558. doi: 10.4049/jimmunol.1700232. Epub 2017 Jun 9.
We employed whole-genome RNA-sequencing to profile mRNAs and both annotated and novel long noncoding RNAs (lncRNAs) in human naive, central memory, and effector memory CD4 T cells. Loci transcribing both lineage-specific annotated and novel lncRNA are adjacent to lineage-specific protein-coding genes in the genome. Lineage-specific novel lncRNA loci are transcribed from lineage-specific typical- and supertranscriptional enhancers and are not multiexonic, thus are more similar to enhancer RNAs. Novel enhancer-associated lncRNAs transcribed from the locus bind the transcription factor NF-κB and enhance binding of NF-κB to the genomic locus. Depletion of the annotated lncRNA, IFNG-AS1, or one enhancer-associated lncRNA abrogates expression by memory T cells, indicating these lncRNAs have biologic function.
我们采用全基因组RNA测序技术，对人类初始、中枢记忆和效应记忆CD4 T细胞中的mRNA以及注释和新发现的长链非编码RNA（lncRNA）进行分析。转录谱系特异性注释lncRNA和新lncRNA的基因座在基因组中与谱系特异性蛋白质编码基因相邻。谱系特异性新lncRNA基因座由谱系特异性典型和超级转录增强子转录而来，且不是多外显子的，因此更类似于增强子RNA。从该基因座转录的新的增强子相关lncRNA与转录因子NF-κB结合，并增强NF-κB与基因组基因座的结合。注释的lncRNA IFNG-AS1或一种增强子相关lncRNA的缺失会消除记忆T细胞的表达，表明这些lncRNA具有生物学功能。
