On the Relationships between LncRNAs and Other Orchestrating Regulators: Role of the Circadian System

Abstract

Numerous lncRNAs exhibit circadian rhythms, sometimes with high amplitudes. Therefore, they are controlled by cellular circadian oscillators. However, they also seem to influence circadian clocks, as shown by the important core oscillator gene Per2, at which antiphasic rhythms of Per2 mRNA and its antisense lncRNA are generated. Circadian cycles have also been described for enhancer and super-enhancer lncRNAs. Various lncRNAs are involved in the generation of the rhythm in the pineal gland, which secretes the circadian regulator molecule, melatonin. This compound acts pleiotropically in presumably all tissues and nucleate cells. At least, some of its effects are mediated by sirtuin 1 (SIRT1). SIRT1 enhances circadian amplitudes as an accessory oscillator component and participates in numerous regulation mechanisms. The interrelated actions of circadian oscillators, melatonin and SIRT1 apparently control at least 30% of all coding genes, processes that involve numerous lncRNAs.

Melatonin in macrophage biology: Current understanding and future perspectives

“…More recently, melatonin was also shown to change the contents of exosomes . These cell‐derived membrane vehicles of 30‐100 nm in diameter carry cargos of miRNAs, miRNA‐sponging lncRNAs (long ncRNAs), and circRNAs (circular RNAs), sometimes DNA, proteins, lipids, and metabolites and mediate intercellular communication by transfer of their contents to recipient cells . Exosomes can change macrophage phenotypes; hence, it will be interesting to study whether exosomes (especially exosomal cargos such as miRNAs, lncRNAs and metabolites) are associated with melatonin‐mediated macrophage polarization.…”

“…132,188 These cell-derived membrane vehicles of 30-100 nm in diameter carry cargos of miRNAs, miRNAsponging lncRNAs (long ncRNAs), and circRNAs (circular RNAs), sometimes DNA, proteins, lipids, and metabolites and mediate intercellular communication by transfer of their contents to recipient cells. 268,269 Exosomes can change macrophage phenotypes; hence, it will be interesting to study whether exosomes (especially exosomal cargos such as miRNAs, lncRNAs and metabolites) are associated with melatonin-mediated macrophage polarization. Besides, it will be worth to explore the interactions between melatonin and other classic molecular regulators (eg, c-MYC), which mediate macrophage phenotypes.…”

Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks

“…This is especially the case in most microRNAs (miRNAs), which target mRNAs, and snoRNAs (small nucleolar RNAs), which are involved in RNA processing [ 207 , 208 ]. Other categories of RNAs such as eRNAs (enhancer RNAs) or super-enhancer lncRNAs (super enhancer long noncoding RNAs) directly interact with the chromatin and even with DNA [ 209 ]. piRNAs (PIWI-interacting RNAs) silence transposable elements via both transcriptional and posttranscriptional mechanisms [ 210 ].…”

“…They may either positively or negatively regulate gene expression, which has been even observed in their subgroup of asRNAs (antisense RNAs). Moreover, various lncRNAs are precursors of miRNAs or snoRNAs [ 209 ]. Moreover, many lncRNAs and circRNAs (circular RNAs) serve as miRNA sponges and gain particular relevance in the transmission of intercellular signals by exosomes and ectosomes [ 209 , 211 , 212 ].…”

“…Moreover, various lncRNAs are precursors of miRNAs or snoRNAs [ 209 ]. Moreover, many lncRNAs and circRNAs (circular RNAs) serve as miRNA sponges and gain particular relevance in the transmission of intercellular signals by exosomes and ectosomes [ 209 , 211 , 212 ]. With regard to melatonin, numerous ncRNAs of different categories were shown to be influenced by this pleiotropic regulator [ 209 , 213 , 214 , 215 ].…”