Abstract
The non-coding genome has previously been regarded as “junk” DNA; however, emerging evidence suggests that the non-coding genome accounts for some of the greater biological complexity observed in mammals. Research into long non-coding RNAs (lncRNAs) has gathered speed in recent years, and a growing body of evidence has implicated lncRNAs in a vast range of cellular functions including gene regulation, chromosome organisation and splicing. T helper cells offer an ideal platform for the study of lncRNAs given they function as part of a complex cellular network and undergo remarkable and finely regulated gene expression changes upon antigenic stimulation. Using various knock down and RNA interaction studies several lncRNAs have been shown to be crucial for T helper cell differentiation, activation and function. Given that RNA targeting therapeutics are rapidly gaining attention, further understanding the mechanistic role of lncRNAs in a T helper context is an exciting area of research, as it may unearth a wide range of new candidate targets for treatment of CD4+ mediated pathologies.
Highlights
Mammalian cells are capable of transcribing approximately 80% of their genome [1,2]
This suggests that non-coding transcripts may account for some of the greater complexity seen in mammals
GATA3-AS1 could not induce a Th2 phenotype in the absence of factors such as MAF, these findings provide strong evidence that the long non-coding RNAs (lncRNAs) GATA3-AS1 plays an essential role in modifying the chromatin landscape of GATA3 and GATA3-AS1, in addition to regulating the expression of GATA3 and Th2 effector cytokines IL-5 and IL-13 [27]
Summary
Mammalian cells are capable of transcribing approximately 80% of their genome [1,2]. Historically, protein coding genes have been the focus of extensive study; the fully spliced, protein-coding transcript isoforms of these genes comprise just above 2% of the genome [3]. The exact function or lack thereof is not known for all of these lncRNA genes, those which have been studied can be classified on their mode of action as cis and/or trans acting lncRNA, through modular interactions with RNA, DNA and proteins [5,8]. Cis acting lncRNAs function by interacting with genes neighbouring their site of transcription and can help localise epigenetic modifiers to these locations [9]. 98.5% of the human genome is comprised of non-coding DNA, contrasting to 25–50% in simple eukaryotes, and >50% in complex fungi and plants [11]. The unique expression profiles of lncRNAs in different T cell subsets suggests that lncRNAs have critical roles in Th cell function during homeostasis and disease
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