CyCoNP lncRNA establishes cis and trans RNA-RNA interactions to supervise neuron physiology.

The combination of morphogenetic and transcription factors together with the synergic aid of noncoding RNAs and their cognate RNA binding proteins contribute to shape motor neurons (MN) identity. Here, we extend the noncoding perspective of human MN, by detailing the molecular and biological activity of CyCoNP (as Cytoplasmic Coordinator of Neural Progenitors) a highly expressed and MN-enriched human lncRNA. Through in silico prediction, in vivo RNA purification and loss of function experiments followed by RNA-sequencing, we found that CyCoNP sustains a specific neuron differentiation program, required for the physiology of both neuroblastoma cells and hiPSC-derived MN, which mainly involves miR-4492 and NCAM1 mRNA. We propose a novel lncRNA-mediated 'dual mode' of action, in which CyCoNP acts in trans as a classical RNA sponge by sequestering miR-4492 from its pro-neuronal targets, including NCAM1 mRNA, and at the same time it plays an additional role in cis by interacting with NCAM1 mRNA and regulating the availability and localization of the miR-4492 in its proximity. These data highlight novel insights into the noncoding RNA-mediated control of human neuron physiology and point out the importance of lncRNA-mediated interactions for the spatial distribution of regulatory molecules.

TGS1 impacts snRNA 3'-end processing, ameliorates survival motor neuron-dependent neurological phenotypes in vivo and prevents neurodegeneration.

Trimethylguanosine synthase 1 (TGS1) is a highly conserved enzyme that converts the 5'-monomethylguanosine cap of small nuclear RNAs (snRNAs) to a trimethylguanosine cap. Here, we show that loss of TGS1 in Caenorhabditis elegans, Drosophila melanogaster and Danio rerio results in neurological phenotypes similar to those caused by survival motor neuron (SMN) deficiency. Importantly, expression of human TGS1 ameliorates the SMN-dependent neurological phenotypes in both flies and worms, revealing that TGS1 can partly counteract the effects of SMN deficiency. TGS1 loss in HeLa cells leads to the accumulation of immature U2 and U4atac snRNAs with long 3' tails that are often uridylated. snRNAs with defective 3' terminations also accumulate in Drosophila Tgs1 mutants. Consistent with defective snRNA maturation, TGS1 and SMN mutant cells also exhibit partially overlapping transcriptome alterations that include aberrantly spliced and readthrough transcripts. Together, these results identify a neuroprotective function for TGS1 and reinforce the view that defective snRNA maturation affects neuronal viability and function.

catRAPID omics v2.0: going deeper and wider in the prediction of protein-RNA interactions.

Prediction of protein-RNA interactions is important to understand post-transcriptional events taking place in the cell. Here we introduce catRAPID omics v2.0, an update of our web server dedicated to the computation of protein-RNA interaction propensities at the transcriptome- and RNA-binding proteome-level in 8 model organisms. The server accepts multiple input protein or RNA sequences and computes their catRAPID interaction scores on updated precompiled libraries. Additionally, it is now possible to predict the interactions between a custom protein set and a custom RNA set. Considerable effort has been put into the generation of a new database of RNA-binding motifs that are searched within the predicted RNA targets of proteins. In this update, the sequence fragmentation scheme of the catRAPID fragment module has been included, which allows the server to handle long linear RNAs and to analyse circular RNAs. For the top-scoring protein-RNA pairs, the web server shows the predicted binding sites in both protein and RNA sequences and reports whether the predicted interactions are conserved in orthologous protein-RNA pairs. The catRAPID omics v2.0 web server is a powerful tool for the characterization and classification of RNA-protein interactions and is freely available at http://service.tartaglialab.com/page/catrapid_omics2_group along with documentation and tutorial.

Monitoring and in vivo ecotoxicological evaluation of surface water quality in Umbria and Tuscany, Italy.

New Zealand White male rabbits have been watered for 45 days with surface water taken from three sites on Lake Trasimeno (Umbria, Italy) and from two artificial reservoirs along the Tiber River, one located on the upper tract of the river, just at the border between the regions of Tuscany and Umbria, and the other at the southernmost end of the Tiber Umbrian tract, just before it leaves Umbria. The detoxifying enzymatic activity (EROD) in rabbits was evaluated and used as an indicator of the chemical contamination of surface water due to various classes of micropollutants including organochlorinate pesticides (OCPs) and polycyclic aromatic hydrocarbons (PAHs). The comparison between EROD values and the concentrations of organic micropollutant found in the water matrices showed that MFO hepatic activity in the rabbits is a sensitive, measurable biological parameter for quantitatively evaluating the presence of xenobiotic compounds in the environment. It can therefore be used as a sufficiently accurate method for evaluating in vivo surface water quality in ecotoxicological screening models over vast areas.