Existing compendia of non-coding RNA (ncRNA) are incomplete, in part because they are derived almost exclusively from small and polyadenylated RNAs. Here we present a more comprehensive atlas of the human transcriptome, which includes small and polyA RNA as well as total RNA from 300 human tissues and cell lines. We report thousands of previously uncharacterized RNAs, increasing the number of documented ncRNAs by approximately 8%. To infer functional regulation by known and newly characterized ncRNAs, we exploited pre-mRNA abundance estimates from total RNA sequencing, revealing 316 microRNAs and 3,310 long non-coding RNAs with multiple lines of evidence for roles in regulating protein-coding genes and pathways. Our study both refines and expands the current catalog of human ncRNAs and their regulatory interactions. All data, analyses and results are available for download and interrogation in the R2 web portal, serving as a basis for future exploration of RNA biology and function.
CD1d‐restricted invariant natural killer T (iNKT) cells constitute a common glycolipid‐reactive innate‐like T‐cell subset with a broad impact on innate and adaptive immunity. While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous CD1d‐dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum (ER) stress in APCs is a potent inducer of CD1d‐dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol‐requiring enzyme‐1a (IRE1α) and protein kinase R‐like ER kinase (PERK). Surprisingly, the neutral but not the polar lipids generated within APCs undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses through induction of distinct classes of neutral lipids.
Asthma is a very heterozygous disease, divided in subtypes, such as eosinophilic and neutrophilic asthma. Phenotyping and endotyping of patients, especially patients with severe asthma who are refractory to standard treatment, are crucial in asthma management and are based on a combination of clinical and biological features. Nevertheless, the quest remains to find better biomarkers that distinguish asthma subtypes in a more clear and objective manner and to find new therapeutic targets to treat people with therapy-resistant asthma. In the past, research to identify asthma subtypes mainly focused on expression profiles of protein-coding genes. However, advances in RNA-sequencing technologies and the discovery of non-coding RNAs as important post-transcriptional regulators have provided an entire new field of research opportunities in asthma. This review focusses on long non-coding RNAs (lncRNAs) in asthma; these are non-coding RNAs with a length of more than 200 nucleotides. Many lncRNAs are differentially expressed in asthma, and several have been associated with asthma severity or inflammatory phenotype. Moreover, in vivo and in vitro functional studies have identified the mechanisms of action of specific lncRNAs. Although lncRNAs remain not widely studied in asthma, the current studies show the potential of lncRNAs as biomarkers and therapeutic targets as well as the need for further research.
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