RNAs adopt specific structures in order to perform their biological activities. The structure of RNA is an important layer of gene expression regulation, and can impact a plethora of cellular processes, starting with transcription, RNA processing, and translation, and ending with RNA turnover. The development of high-throughput technologies has enabled a deeper insight into the sophisticated interplay between the structure of the cellular transcriptome and the living cells environment. In this review, we present the current view on the RNA structure in vivo resulting from the most recent transcriptome-wide studies in different organisms, including mammalians, yeast, plants, and bacteria. We focus on the relationship between the mRNA structure and translation, mRNA stability and degradation, protein binding, and RNA posttranscriptional modifications.

Long terminal repeat (LTR)-retrotransposons constitute a significant part of eukaryotic genomes and influence their function and evolution. Like other RNA viruses, LTR-retrotransposons efficiently utilize their RNA genome to interact with host cell machinery during replication. Here, we provide the first genome-wide RNA secondary structure model for a LTR-retrotransposon in living cells. Using SHAPE probing, we explore the secondary structure of the yeast Ty1 retrotransposon RNA genome in its native in vivo state and under defined in vitro conditions. Comparative analyses reveal the strong impact of the cellular environment on folding of Ty1 RNA. In vivo, Ty1 genome RNA is significantly less structured and more dynamic but retains specific well-structured regions harboring functional cis-acting sequences. Ribosomes participate in the unfolding and remodeling of Ty1 RNA, and inhibition of translation initiation stabilizes Ty1 RNA structure. Together, our findings support the dual role of Ty1 genomic RNA as a template for protein synthesis and reverse transcription. This study also contributes to understanding how a complex multifunctional RNA genome folds in vivo, and strengthens the need for studying RNA structure in its natural cellular context.

The cannabinoid receptor type 1 (CB1R), a G protein-coupled receptor (GPCR), plays an essential role in the control of many physiological processes such as hunger, memory loss, gastrointestinal activity, catalepsy, fear, depression, and chronic pain. Therefore, it is an attractive target for drug discovery to manage pain, neurodegenerative disorders, obesity, and substance abuse. However, the psychoactive adverse effects, generated by CB1R activation in the brain, limit the use of the orthosteric CB1R ligands as drugs. The discovery of CB1R allosteric modulators during the last decade provided new tools to target the CB1R. Moreover, application of the site-directed mutagenesis in combination with advanced physical methods, especially X-ray crystallography and computational modeling, has opened new horizons for understanding the complexity of the structure, function, and activity of cannabinoid receptors. In this paper, we present the latest advances in research on the CB1R, its allosteric modulation and allosteric ligands, and their translational potential. We focused on structural essentials of the cannabinoid 1 receptor- ligand (drug) interactions, as well as modes of CB1R signaling regulation.

The endocannabinoid system (ECS) consists of the endocannabinoids, cannabinoid receptors and the enzymes that synthesize and degrade endocannabinoids. The whole EC system plays an important role in the proper functioning of the central and autonomic nervous system. ECS is involved in the regulation of the body energy and in the functioning of the endocrine system. It can affect on the regulation of emotional states, motoric movement, operations of the endocrine, immune and digestive system. Many of the effects of cannabinoids are mediated by G coupled –protein receptors: CB1, CB2 and GPR55 but also of transient receptor potential channels (TRPs) which not only induce the sensation of pain but also support inflammation via secretion of pro-inflammatory neuropeptides. In this review work we briefly summarize the role and action of cannabinoid receptors CB1 and CB2, protein-coupled receptor 55 (GPR55) and transient receptor potential vanilloid 1 (TRPV1).