MicroRNAs Micromanage Themselves

Abstract

Since their discovery not long ago, microRNAs (miRNAs) have been extensively studied in hundreds of laboratories around the world. Initially thought of as merely cytoplasmic repressors of mRNA expression, it has since become more apparent that they also play regulatory roles in the nucleus. A recent study published in Nature introduces novel concepts in both miRNA regulation and function by showing that the let-7 miRNA regulates its own expression.

The temporal expression of circulating microRNAs after acute experimental pain in humans

“…The present results with detected miRNA modifications 24 hours after an acute pain insult suggest an alteration not only due to the experimental pain but may also point toward an effect of miRNAs on self‐regulation (Jiao & Slack, 2012; Zisoulis et al, 2012) and homeostatic plasticity (Dubes et al, 2019). It is currently unclear whether the changes caused by experimental muscle pain can be identified only in the alteration in a short time (30 minutes) or the effect could include the changes continuing to develop up to 24 hours after the insult.…”

“…In this study, the miRNA alterations found 24 hours after stimulation, could then be explained by a regulatory neuronal pathway in which discovered miRNA are potentially involved. It is important to point out the high variability in the expressed transcripts, which might indicate a self‐regulation mechanism of miRNAs but also suggest a canonical pathway of RNA messenger regulation is driven by these molecules (Jiao & Slack, 2012; O'Brien et al, 2018). In the present study, only two miRNAs showed a time‐stable altered expression in the pain group when compared with controls.…”

Are spliced ncRNA host genes distinct classes of lncRNAs?

“…Other, more dynamical effects, such as a potential contribution of host gene abundance to the regulation of payload (Baskerville and Bartel 2005;Warner et al 2018), on the other hand, cannot be assessed at sequence level alone and thus have to remain a topic for future research. Similarly, indirect links between miRNAs and sdRNAs (snoRNA-derived sRNAs) on factors that regulate hostgene transcription as well as direct interactions of the payload with the hostgene, known, e.g., in the case of let-7 (Jiao and Slack 2012;Minchington et al 2020) are beyond the scope of this contribution. Our data do indicate, however, that such feedback will be realized by a diversity of mechanisms, rather than a single ubiquitous paradigm.…”

Innate Immune Memory in Macrophages

“… 214 The miRNA-induced silencing complexes (miRISCs) involve interactions of the conserved GW182 proteins (named after the glycine and tryptophan repeats and the molecular weight) with the argonaute proteins (discovered in Arabidopsis thaliana ) and downstream deadenylases. 215 These protein–protein interactions, in turn, increase (a) biogenesis of small RNAs 216 ; (b) insertion of tryptophan residues into hydrophobic pockets on the surface of argonaute proteins 217 ; (c) displacement of the translation initiation factors 4A 218 ; and/or (d) recruitment of the translational repressor and decapping of the activator DEAD box protein 6. 219 …”