651 research outputs found
Computational characterization of alternative splicing events in coding and non-coding genes
No full textAlternative splicing (AS) represents an effective way to expand the proteome, and thus the biological complexity, without having to create and evolve new genes. Anecdotal evidence of the involvement of alternative splicing in the regulation of protein-protein interactions has been reported by several studies. AS events have been shown to significantly occur in regions where a protein interaction domain or a short linear motif is present. Several AS variants show partial or complete loss of interface residues, suggesting that AS can play a major role in the interaction regulation by selectively targeting the protein binding sites. In the first part of my PhD work I performed a statistical analysis of the alternative splicing of a non-redundant data set of human protein-protein interfaces known at molecular level to determine the importance of this way of modulation of protein-protein interactions through AS. I demonstrated that the alternative splicingmediated partial removal of both heterodimeric and homodimeric binding sites occurs at lower frequencies than expected, and this holds true even if I consider only those isoforms whose sequence is less different from that of the canonical protein and which therefore allow to selectively regulate functional regions of the protein. On the other hand, large removals of the binding site are not significantly prevented, possibly because they are associated to drastic structural changes of the protein. The observed protection of the binding sites from AS is not preferentially directed towards putative hot spot interface residues, and is widespread to all protein functional classes. Using the same procedure as that applied for proteinprotein interactions, I also evaluated the importance of AS-mediated removal of protein-ligand binding sites, obtained from three-dimensional structures of human proteins. Again, I observed that AS tends to avoid partial removal of such sites, while being quite indifferent to complete or near-complete deletions. This tendency does not depend on the size of the binding site. The choice of the AS pattern of a gene is thus conditioned by constraints imposed by the three-dimensional structure of the protein products.
Alternative splicing is not observed only in protein-coding genes: many long non-coding RNA (lncRNAs) have two or more transcript isoforms. Since these transcripts are not translated, the differential usage of splice sites cannot be influenced by structural constraints, except for those related to the RNA folding. Even if AS occurs in about a quarter of lncRNA genes, little is known about its role in the regulation of lncRNA function and stability, mainly because few lncRNAs have been functionally characterized. The aim of the second half of my PhD work was to study the alternative splicing of lncRNA genes. First, I analyzed the evolutionary conservation of lncRNA alternatively spliced sequences (and their flanking regions) and I found that their pattern of conservation is similar to that showed in protein-coding genes; this suggests that AS of lncRNA genes is as important as that of protein-coding genes, at least from an evolutionary standpoint. To study the impact of AS on lncRNA functional sites, I assembled a data set of proteinRNA interaction sites by reanalysing published CLIP-Seq, RIP-Seq and RIPChip experiments. The results of this reanalysis work will be stored in a public database of protein-RNA interactions detected via high-throughput methods
Revealing protein-lncRNA interaction
No full textLong non-coding RNAs (lncRNAs) are associated to a plethora of cellular functions, most of which require the interaction with one or more RNA-binding proteins (RBPs); similarly, RBPs are often able to bind a large number of different RNAs. The currently available knowledge is already drawing an intricate network of interactions, whose deregulation is frequently associated to pathological states. Several different techniques were developed in the past years to obtain protein-RNA binding data in a high-throughput fashion. In parallel, in silico inference methods were developed for the accurate computational prediction of the interaction of RBP-lncRNA pairs. The field is growing rapidly, and it is foreseeable that in the near future, the protein-lncRNA interaction network will rise, offering essential clues for a better understanding of lncRNA cellular mechanisms and their disease-associated perturbations
Prediction of protein-RNA interactions from single-cell transcriptomic data
No full textProteins are crucial in regulating every aspect of RNA life, yet understanding their interactions with coding and noncoding RNAs remains limited. Experimental studies are typically restricted to a small number of cell lines and a limited set of RNA-binding proteins (RBPs). Although computational methods based on physico-chemical principles can predict protein-RNA interactions accurately, they often lack the ability to consider cell-type-specific gene expression and the broader context of gene regulatory networks (GRNs). Here, we assess the performance of several GRN inference algorithms in predicting protein-RNA interactions from single-cell transcriptomic data, and propose a pipeline, called scRAPID (single-cell transcriptomic-based RnA Protein Interaction Detection), that integrates these methods with the catRAPID algorithm, which can identify direct physical interactions between RBPs and RNA molecules. Our approach demonstrates that RBP-RNA interactions can be predicted from single-cell transcriptomic data, with performances comparable or superior to those achieved for the well-established task of inferring transcription factor-target interactions. The incorporation of catRAPID significantly enhances the accuracy of identifying interactions, particularly with long noncoding RNAs, and enables the identification of hub RBPs and RNAs. Additionally, we show that interactions between RBPs can be detected based on their inferred RNA targets. The software is freely available at https://github.com/tartaglialabIIT/scRAPID
The Pottesman Collection in the British Museum. Early Dynastic and Sargonic administrative texts. With an Appendix on a Palmyrene Inscription
No full textEdizione, trascrizione, traduzione e commento di un frammento di iscrizione palmirena inedita presente nella collezione Pottesman del British Museum (Appendice Agostini).The British Museum houses a small collection of six cuneiform tablets and a Palmyrene dedicatory inscription purchased in 1987 from the private collection of Solomon Pottesman. The aim of the present contribution is to provide a catalog of this lot and an edition of the so far unpublished cuneiform texts. In the appendix, Alessio Agostini added the edition of the Palmyrene inscription, which would have otherwise gone beyond the capabilities of the present author
Recensione di Cecilia Falchini (2023). Ruperto di deutz - Un’intima familiarità. Antologia, Edizioni Qiqajon (Comunità di Bose), Magnano (Bi), 281 pp.
No full textReview of Cecilia Falchini (2023). Ruperto di deutz - Un’intima familiarità. Antologia, Edizioni Qiqajon (Comunità di Bose), Magnano (Bi), 281 pp.
Author: Alessio MagogaRecensione di Cecilia Falchini (2023). Ruperto di deutz - Un’intima familiarità. Antologia, Edizioni Qiqajon (Comunità di Bose), Magnano (Bi), 281 pp.
Autor: Alessio Magog
FUS Alters circRNA Metabolism in Human Motor Neurons Carrying the ALS-Linked P525L Mutation
No full textDeregulation of RNA metabolism has emerged as one of the key events leading to the degeneration of motor neurons (MNs) in Amyotrophic Lateral Sclerosis (ALS) disease. Indeed, mutations on RNA-binding proteins (RBPs) or on proteins involved in aspects of RNA metabolism account for the majority of familiar forms of ALS. In particular, the impact of the ALS-linked mutations of the RBP FUS on many aspects of RNA-related processes has been vastly investigated. FUS plays a pivotal role in splicing regulation and its mutations severely alter the exon composition of transcripts coding for proteins involved in neurogenesis, axon guidance, and synaptic activity. In this study, by using in vitro-derived human MNs, we investigate the effect of the P525L FUS mutation on non-canonical splicing events that leads to the formation of circular RNAs (circRNAs). We observed altered levels of circRNAs in FUSP525L MNs and a preferential binding of the mutant protein to introns flanking downregulated circRNAs and containing inverted Alu repeats. For a subset of circRNAs, FUSP525L also impacts their nuclear/cytoplasmic partitioning, confirming its involvement in different processes of RNA metabolism. Finally, we assess the potential of cytoplasmic circRNAs to act as miRNA sponges, with possible implications in ALS pathogenesis
catRAPID omics v2.0: going deeper and wider in the prediction of protein–RNA interactions
No full textPrediction 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
Handheld-Impedance-Measurement System with seven-decade capability and potentiostatic function
No full textThis paper describes design and test of a new impedance-measurement system for nonlinear devices that exhibits a seven-decade range and works down to a frequency of 0.01 Hz. The system is specifically designed for electrochemical measurements, but the proposed architecture can be employed in many other fields where flexible signal generation and analysis are required. The system employs an unconventional signal generator based on two pulsewidth modulation (PWM) oscillators and an autocalibration system that allows uncertainties of less than 3% to be obtained over a range of 1 kΩ to 100 GΩ. A synchronous demodulation processing allows the noise superimposed to the low-amplitude input signals to be made negligibl
DBATE: database of alternative transcripts expression
No full textThe use of high-throughput RNA sequencing technology (RNA-seq) allows whole transcriptome analysis, providing an unbiased and unabridged view of alternative transcript expression. Coupling splicing variant-specific expression with its functional inference is still an open and difficult issue for which we created the DataBase of Alternative Transcripts Expression (DBATE), a web-based repository storing expression values and functional annotation of alternative splicing variants. We processed 13 large RNA-seq panels from human healthy tissues and in disease conditions, reporting expression levels and functional annotations gathered and integrated from different sources for each splicing variant, using a variant-specific annotation transfer pipeline. The possibility to perform complex queries by cross-referencing different functional annotations permits the retrieval of desired subsets of splicing variant expression values that can be visualized in several ways, from simple to more informative. DBATE is intended as a novel tool to help appreciate how, and possibly why, the transcriptome expression is shaped. DATABASE URL: http://bioinformatica.uniroma2.it/DBATE/
El Tlacuache Núm. 16 (2001). 16 Año 1 (2001) octubre. El Tlacuache
No full text- ¿Entre la Guerra Santa y la Cruzada? por Aníbal Quijano. - Nuestro patrimonio desconocido por Teresita Loera y Anaite Monterforte. - El Yahutli por Margarita Avilés y Macrina Fuentes. - Haciendas por Carlos Fernando Alessio Robles
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