Tumors carrying BRAF-mutations over-express NAMPT that is genetically amplified and possesses oncogenic properties.

Background: Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis, is up-regulated in several cancers, including metastatic melanoma (MM). The BRAF oncogene is mutated in different cancer types, among which MM and thyroid carcinoma (THCA) are prominent. Drugs targeting mutant BRAF are effective, especially in MM patients, even though resistance rapidly develops.

RNA Post-Transcriptional Modification Mapping Data Analysis Using RNA Framework.

RNA post-transcriptional modifications (PTMs) are progressively gaining relevance in the study of coding-independent functions of RNA. RNA PTMs act as dynamic regulators of several aspects of the RNA physiology, from translation to half-life. Rising interest is supported by the advance of high-throughput techniques enabling the detection of these modifications on a transcriptome-wide scale.

Genome-scale deconvolution of RNA structure ensembles.

RNA structure heterogeneity is a major challenge when querying RNA structures with chemical probing. We introduce DRACO, an algorithm for the deconvolution of coexisting RNA conformations from mutational profiling experiments. Analysis of the SARS-CoV-2 genome using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and DRACO, identifies multiple regions that fold into two mutually exclusive conformations, including a conserved structural switch in the 3' untranslated region.

Structure and regulation of coronavirus genomes: state-of-the-art and novel insights from SARS-CoV-2 studies.

Coronaviruses (CoV) are positive-sense single-stranded RNA viruses, harboring the largest viral RNA genomes known to date. Apart from the primary sequence encoding for all the viral proteins needed for the generation of new viral particles, certain regions of CoV genomes are known to fold into stable structures, controlling several aspects of CoV life cycle, from the regulation of the discontinuous transcription of subgenomic mRNAs, to the packaging of the genome into new virions. Here we review the current knowledge on CoV RNA structures, discussing it in light of the most recent discoveries made possible by analyses of the SARS-CoV-2 genome.

Genome-wide mapping of SARS-CoV-2 RNA structures identifies therapeutically-relevant elements.

SARS-CoV-2 is a betacoronavirus with a linear single-stranded, positive-sense RNA genome, whose outbreak caused the ongoing COVID-19 pandemic. The ability of coronaviruses to rapidly evolve, adapt, and cross species barriers makes the development of effective and durable therapeutic strategies a challenging and urgent need. As for other RNA viruses, genomic RNA structures are expected to play crucial roles in several steps of the coronavirus replication cycle.

Subcellular Characterization of Nicotinamide Adenine Dinucleotide Biosynthesis in Metastatic Melanoma by Using Organelle-Specific Biosensors.

Nicotinamide adenine dinucleotide (NAD) plays central roles in a wide array of normal and pathological conditions. Inhibition of NAD biosynthesis can be exploited therapeutically in cancer, including melanoma. To obtain quantitation of NAD levels in live cells and to address the issue of the compartmentalization of NAD biosynthesis, we exploited a recently described genetically encoded NAD biosensor (LigA-circularly permutated Venus), which was targeted to the cytosol, mitochondria, and nuclei of A375 melanoma cells, a model of metastatic melanoma (MM).