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Review
. 2016 Jan;99(1):31-44.
doi: 10.1189/jlb.1RI0815-389R. Epub 2015 Nov 4.

Long noncoding RNAs in T lymphocytes

Affiliations
Review

Long noncoding RNAs in T lymphocytes

Thomas M Aune et al. J Leukoc Biol. 2016 Jan.

Abstract

Long noncoding RNAs are recently discovered regulatory RNA molecules that do not code for proteins but influence a vast array of biologic processes. In vertebrates, the number of long noncoding RNA genes is thought to greatly exceed the number of protein-coding genes. It is also thought that long noncoding RNAs drive the biologic complexity observed in vertebrates compared with that in invertebrates. Evidence of this complexity has been found in the T-lymphocyte compartment of the adaptive immune system. In the present review, we describe our current level of understanding of the expression of specific long or large intergenic or intervening long noncoding RNAs during T-lymphocyte development in the thymus and differentiation in the periphery and highlight the mechanisms of action that specific long noncoding RNAs employ to regulate T-lymphocyte function, both in vitro and in vivo.

Keywords: adaptive immunity; epigenetics; lncRNA.

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Figures

Figure 1
Figure 1
Biologic complexity and expansion of genomes. (A) Illustration of humans and worms (Caenorhabditis elegans). (B) Numbers of mRNA genes in genomes of different organisms from different phyla. (C) Genome size in different organisms from different phyla. (D) Organisms from many different phyla produce lncRNAs. (E) Potential number of lncRNAs produced by organisms from different phyla.
Figure 2
Figure 2
Complexity of T‐lymphocyte development and differentiation. iTregs, induced Tregs; Tfh, T follicular helper (cell).
Figure 3
Figure 3
Close proximity of Th cell lineage‐specific mRNA and lncRNA genes to each other in the human genome. Left Y‐axis, percentage of lineage‐specific lncRNA genes the indicated distance from a lineage‐specific mRNA gene; right Y‐axis, percentage of lineage‐specific mRNA genes the indicated distance from a lineage‐specific lncRNA gene.
Figure 4
Figure 4
Illustration of RAD50 and Th2LCRR alternatively spliced exon boundaries. Rectangles represent spliced exons for the indicated transcripts. Black rectangle sequences do not match with other Th2LCRR transcripts; the green rectangle sequence is the shared sequence among all Th2LCRR isoforms; the blue rectangle sequence is a shared sequence among 2 Th2LCRR isoforms; the red rectangle sequence is a shared sequence among 3 Th2LCRR isoforms; orange is shared sequence among each Th2LCRR isoform.
Figure 5
Figure 5
Cartoon model illustrating mechanisms of action of T cell lncRNAs. LncRNA and mRNA genes are depicted by speckled green and red, respectively. Black arrows below indicate orientation of transcription. lncRNAs are depicted by green squiggly line with cargo, either WDR5 or EZH2/LSD1 (blue). Green arrows connect lncRNA gene to the lncRNA or the target of the lncRNA to the mRNA gene (green, activating; red, inhibiting). Yellow stars show locations of H3K4Me marks that favor transcriptional activation, and black “explosions” show locations of H3K27Me marks that suppress transcription of gene targets.
Figure 6
Figure 6
Example of a pipeline for identification and characterization of annotated and novel lncRNAs using whole genome sequencing.

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