Profiles of Long Noncoding RNAs in Human Naive and Memory T Cells

J Immunol. 2017 Jul 15;199(2):547-558. doi: 10.4049/jimmunol.1700232. Epub 2017 Jun 9.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • NF-kappa B
  • RNA, Long Noncoding
  • RNA, Messenger
  • Interferon-gamma