BackgroundADAR enzymes convert adenosines to inosines within double-stranded RNAs, including microRNA (miRNA) precursors, with important consequences on miRNA retargeting and expression. ADAR2 activity is impaired in glioblastoma and its rescue has anti-tumoral effects. However, how ADAR2 activity may impact the miRNome and the progression of glioblastoma is not known.ResultsBy integrating deep-sequencing and array approaches with bioinformatics analyses and molecular studies, we show that ADAR2 is essential to edit a small number of mature miRNAs and to significantly modulate the expression of about 90 miRNAs in glioblastoma cells. Specifically, the rescue of ADAR2 activity in cancer cells recovers the edited miRNA population lost in glioblastoma cell lines and tissues, and rebalances expression of onco-miRNAs and tumor suppressor miRNAs to the levels observed in normal human brain. We report that the major effect of ADAR2 is to reduce the expression of a large number of miRNAs, most of which act as onco-miRNAs. ADAR2 can edit miR-222/221 and miR-21 precursors and decrease the expression of the corresponding mature onco-miRNAs in vivo and in vitro, with important effects on cell proliferation and migration.ConclusionsOur findings disclose an additional layer of complexity in miRNome regulation and provide information to better understand the impact of ADAR2 editing enzyme in glioblastoma. We propose that ADAR2 is a key factor for maintaining edited-miRNA population and balancing the expression of several essential miRNAs involved in cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-014-0575-z) contains supplementary material, which is available to authorized users.

ALS is a devastating and debilitating human disease characterized by the progressive death of upper and lower motor neurons. Although much effort has been made to elucidate molecular determinants underlying the onset and progression of the disorder, the causes of ALS remain largely unknown. In the present work, we have deeply sequenced whole transcriptome from spinal cord ventral horns of post-mortem ALS human donors affected by the sporadic form of the disease (which comprises ~90% of the cases but which is less investigated than the inherited form of the disease). We observe 1160 deregulated genes including 18 miRNAs and show that down regulated genes are mainly of neuronal derivation while up regulated genes have glial origin and tend to be involved in neuroinflammation or cell death. Remarkably, we find strong deregulation of SNAP25 and STX1B at both mRNA and protein levels suggesting impaired synaptic function through SNAP25 reduction as a possible cause of calcium elevation and glutamate excitotoxicity. We also note aberrant alternative splicing but not disrupted RNA editing.

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CoA is an essential cofactor that holds a central role in cell metabolism. Although its biosynthetic pathway is conserved across the three domains of life, the subcellular localization of the eukaryotic biosynthetic enzymes and the mechanism behind the cytosolic and mitochondrial CoA pools compartmentalization are still under debate. In humans, the transport of CoA across the inner mitochondrial membrane has been ascribed to two related genes, SLC25A16 and SLC25A42 whereas in D. melanogaster genome only one gene is present, CG4241, phylogenetically closer to SLC25A42. CG4241 encodes two alternatively spliced isoforms, dPCoAC-A and dPCoAC-B. Both isoforms were expressed in Escherichia coli, but only dPCoAC-A was successfully reconstituted into liposomes, where transported dPCoA and, to a lesser extent, ADP and dADP but not CoA, which was a powerful competitive inhibitor. The expression of both isoforms in a Saccharomyces cerevisiae strain lacking the endogenous putative mitochondrial CoA carrier restored the growth on respiratory carbon sources and the mitochondrial levels of CoA. The results reported here and the proposed subcellular localization of some of the enzymes of the fruit fly CoA biosynthetic pathway, suggest that dPCoA may be synthesized and phosphorylated to CoA in the matrix, but it can also be transported by dPCoAC to the cytosol, where it may be phosphorylated to CoA by the monofunctional dPCoA kinase. Thus, dPCoAC may connect the cytosolic and mitochondrial reactions of the CoA biosynthetic pathway without allowing the two CoA pools to get in contact.

Aiming at meeting consumers’ requirements for healthy foods, dietary needs (vegetarianism, lactose- and gluten-free), as well as the nutrition recommendations of the Health Authorities in terms of protein, fibers and bioactive compounds, the present study proposes a novel yogurt-style snack made with plant-derived ingredients. The biotechnological protocol includes the fermentation of a thermal-treated blend of cereal and legume flours by the selected lactic acid bacteria (LAB) Lactoplantibacillus plantarum DSM33326 and Levilactobacillus brevis DSM33325. The yogurt-style snack was characterized by protein and fiber concentration of 3 and 4%, respectively, and a low-fat content. Compared to the unfermented control, the yogurt-style snack was characterized by a significant higher concentration of free amino acids and lower contents of the antinutritional factors, i.e., phytic acid, condensed tannins, saponins and raffinose (up to 90%) mainly due to the LAB metabolic activity. Hence, an in-vitro protein digestibility of 79% and improvements of all the nutritional indexes related to the quality of the protein fraction (e.g., GABA) were achieved at the end of fermentation. According to the Harvard Medical School recommendations, the novel snack can be potentially classified as low-glycemic index food (53%). Antioxidant properties of the fermented snack were also improved by means of increased the total phenol content and radical scavenging activity. High survival rate of the starter LAB and a commercial probiotic (added to the snack) was found through 30 days storage under refrigerated conditions. The biotechnological protocol to make the novel snack here proposed is suitable for the large-scale application in food industry, giving a platform product with a peculiar and appreciated sensory profile.