Human dyskerin is an evolutively conserved protein that participates in diverse nuclear complexes: the H/ACA snoRNPs, that control ribosome biogenesis, RNA pseudouridylation, and stability of H/ACA snoRNAs; the scaRNPs, that control pseudouridylation of snRNAs; and the telomerase active holoenzyme, which safeguards telomere integrity. The biological importance of dyskerin is further outlined by the fact that its deficiency causes the X-linked dyskeratosis congenita disease, while its over-expression characterizes several types of cancers and has been proposed as prognostic marker. The role of dyskerin in telomere maintenance has widely been discussed, while its functions as H/ACA sno/scaRNP component has been so far mostly overlooked and represent the main goal of this review. Here we summarize how increasing evidence indicates that the snoRNA/microRNA pathways can be interlaced, and that dyskerin-dependent RNA pseudouridylation represents a flexible mechanism able to modulate RNA function in different ways, including modulation of splicing, change of mRNA coding properties, and selective regulation of IRES-dependent translation. We also propose a speculative model that suggests that the dynamics of pre-assembly and nuclear import of H/ACA RNPs are crucial regulatory steps that can be finely controlled in the cytoplasm in response to developmental, differentiative and stress stimuli.

Artificial selection began to override natural selection in domesticated wild boar and other species about 10,000 years ago. The intentional selection of a desired phenotypic trait is a complex process, and comes along with unexpected or even unwanted changes in other traits, because of epistatic gene effects, and ontogenetic con- straints. The loss of brain mass in domestic ungulates is related to selection for reduced reaction to external stimuli. Evolutionary losses in body structures and genes were once considered mostly irreversible, in keeping with Dollo’s law. Here we studied the biochemical and the histological functioning of the free-living pigs (FLPs) olfactory system, to see if and to what extent does FLPs regain a full sense of smell, as compared to the domestic pigs and wild boar Sus scrofa. In our samples both wild boars and FLPs have significantly larger brain per unit mass than domestic pigs, and FLPs’ brains are not significantly smaller than wild boar’s. Similarly, both wild boars and FLPs have signifi- cantly higher cell density than domestic pigs in the olfac- tory mucosa. Yet, at the functional level, olfactory marker protein and neuropeptide Y, both of which are important to the correct functioning of the sense of smell, are fully expressed only in wild boar. These results suggest that FLPs reacquired structural, but not the biochemical capa- bility in their olfactory system

SUMMARY Glutamate receptor auxiliary proteins control receptor distribution and function, ultimately controlling synapse assembly, maturation, and plasticity. At the Drosophila neuromuscular junction (NMJ), a synapse with both pre- and postsynaptic kainate-type glutamate receptors (KARs), we show that the auxiliary protein Neto evolved functionally distinct isoforms to modulate synapse development and homeostasis. Using genetics, cell biology, and electrophysiology, we demonstrate that Neto-α functions on both sides of the NMJ. In muscle, Neto-α limits the size of the postsynaptic receptor field. In motor neurons (MNs), Neto-α controls neurotransmitter release in a KAR-dependent manner. In addition, Neto-α is both required and sufficient for the presynaptic increase in neurotransmitter release in response to reduced postsynaptic sensitivity. This KAR-independent function of Neto-α is involved in activity-induced cytomatrix remodeling. We propose that Drosophila ensures NMJ functionality by acquiring two Neto isoforms with differential expression patterns and activities.

Single‐cell RNA sequencing provides a new approach to an old problem: how to study cellular diversity in complex biological systems. This powerful tool has been instrumental in profiling different cell types and investigating, at the single‐cell level, cell states, functions, and responses. However, mining these data requires new analytical and statistical methods for high‐dimensional analyses that must be customized and adapted to specific goals. Here we present a custom multistage analysis pipeline which integrates modules contained in different R packages to ensure flexible, high‐quality RNA‐seq data analysis. We describe this workflow step by step, providing the codes, explaining the rationale for each function, and discussing the results and the limitations. We apply this pipeline to analyze different datasets of Drosophila larval ventral cords, identifying and describing rare cell types, such as astrocytes and neuroendocrine cells. This multistage analysis pipeline can be easily implemented by both novice and experienced scientists interested in neuronal and/or cellular diversity beyond the Drosophila model system. © 2021 US Government.