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J Immunol ; 199(2): 547-558, 2017 07 15.
Article in English | MEDLINE | ID: mdl-28600289

ABSTRACT

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 IFNG locus bind the transcription factor NF-κB and enhance binding of NF-κB to the IFNG genomic locus. Depletion of the annotated lncRNA, IFNG-AS1, or one IFNG enhancer-associated lncRNA abrogates IFNG expression by memory T cells, indicating these lncRNAs have biologic function.


Subject(s)
Immunologic Memory , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , T-Lymphocytes/immunology , Cell Lineage , Genome, Human , Humans , Interferon-gamma/genetics , Interferon-gamma/immunology , NF-kappa B/metabolism , RNA, Messenger/genetics , Regulatory Sequences, Nucleic Acid , Sequence Analysis, RNA
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