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Natural antisense transcripts, because of their potential to form double-stranded RNA (dsRNA) molecules, recently emerged as a mechanism acting on eukaryotic gene regulation at multiple levels. CHRNA3 and CHRNA5, coding for alpha3 and alpha5 subunits of the neuronal nicotinic acetylcholine receptor, have been reported to overlap at their 3'ends in human and bovine genomes. In the present paper, four CHRNA3 and three CHRNA5 human transcripts were characterised, leading to the identification of different antisense complementary regions. Since the two genes are coexpressed in some neuronal and non-neuronal tissues, we ventured on the in vivo identification of RNA-RNA duplexes in both humans and cattle. Using an RNase protection-based approach, CHRNA3/CHRNA5 duplexes were detected in human neuroblastoma SY5Y cells, but not in bovine cerebellum. A semi-quantitative analysis of overlapping transcript levels was performed by real-time RT-PCR. Possible consequences of sense-antisense interaction are discussed.

How gene expression is controlled to preserve human T cell quiescence is poorly understood. Here we show that non-canonical splicing variants containing long interspersed nuclear element 1 (LINE1) enforce naive CD4+ T cell quiescence. LINE1-containing transcripts are derived from CD4+ T cell-specific genes upregulated during T cell activation. In naive CD4+ T cells, LINE1-containing transcripts are regulated by the transcription factor IRF4 and kept at chromatin by nucleolin; these transcripts act in cis, hampering levels of histone 3 (H3) lysine 36 trimethyl (H3K36me3) and stalling gene expression. T cell activation induces LINE1-containing transcript downregulation by the splicing suppressor PTBP1 and promotes expression of the corresponding protein-coding genes by the elongating factor GTF2F1 through mTORC1. Dysfunctional T cells, exhausted in vitro or tumor-infiltrating lymphocytes (TILs), accumulate LINE1-containing transcripts at chromatin. Remarkably, depletion of LINE1-containing transcripts restores TIL effector function. Our study identifies a role for LINE1 elements in maintaining T cell quiescence and suggests that an abundance of LINE1-containing transcripts is critical for T cell effector function and exhaustion.