https://www.normalesup.org/~vorgogoz/articles/D.pachea-references/alternative-splicing/Stamm2005-alternative-splicing-review.pdf

Function of alternative splicing.

Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants.

ReviewFunction of alternative splicing

In the process of establishing more and more complete annotations of eukaryotic genomes, a constantly growing number of alternative splicing (AS) events has been reported over the last decade. Consequently, the increasing transcript coverage also revealed the real complexity of some variations in the exon–intron structure between transcript variants and the need for computational tools to address ‘complex’ AS events. ASTALAVISTA (alternative splicing transcriptional landscape visualization tool) employs an intuitive and complete notation system to univocally identify such events. The method extracts AS events dynamically from custom gene annotations, classifies them into groups of common types and visualizes a comprehensive picture of the resulting AS landscape. Thus, ASTALAVISTA can characterize AS for whole transcriptome data from reference annotations (GENCODE, REFSEQ, ENSEMBL) as well as for genes selected by the user according to common functional/structural attributes of interest: http://genome.imim.es/astalavista

ASTALAVISTA: dynamic and flexible analysis of alternative splicing events in custom gene datasets.

The tumour suppressor p53 is the most frequently mutated gene in human cancer. Reactivation of mutant p53 by small molecules is an exciting potential cancer therapy. Although several compounds restore wild-type function to mutant p53, their binding sites and mechanisms of action are elusive. Here computational methods identify a transiently open binding pocket between loop L1 and sheet S3 of the p53 core domain. Mutation of residue Cys124, located at the centre of the pocket, abolishes p53 reactivation of mutant R175H by PRIMA-1, a known reactivation compound. Ensemble-based virtual screening against this newly revealed pocket selects stictic acid as a potential p53 reactivation compound. In human osteosarcoma cells, stictic acid exhibits dose-dependent reactivation of p21 expression for mutant R175H more strongly than does PRIMA-1. These results indicate the L1/S3 pocket as a target for pharmaceutical reactivation of p53 mutants.

/pdf/computational-identification-of-a-transiently-open-l1-s3-2wl8x0wfgm.pdf

Computational identification of a transiently open L1/S3 pocket for reactivation of mutant p53

The Protein Model Database (PMDB) is a public resource aimed at storing manually built 3D models of proteins The database is designed to provide access to models published in the scientific literature, together with validating experimental data It is a relational database and it currently contains >74,000 models for approximately 240 proteins The system is accessible at http://wwwcaspurit/PMDB and allows predictors to submit models along with related supporting evidence and users to download them through a simple and intuitive interface Users can navigate in the database and retrieve models referring to the same target protein or to different regions of the same protein Each model is assigned a unique identifier that allows interested users to directly access the data

/pdf/the-pmdb-protein-model-database-4xrt78x7yq.pdf

The PMDB Protein Model Database.

Alternative splicing (AS) is now emerging as a major mechanism contributing to the expansion of the transcriptome and proteome complexity of multicellular organisms. The fact that a single gene locus may give rise to multiple mRNAs and protein isoforms, showing both major and subtle structural variations, is an exceptionally versatile tool in the optimization of the coding capacity of the eukaryotic genome. The huge and continuously increasing number of genome and transcript sequences provides an essential information source for the computational detection of genes AS pattern. However, much of this information is not optimally or comprehensively used in gene annotation by current genome annotation pipelines. We present here a web resource implementing the ASPIC algorithm which we developed previously for the investigation of AS of user submitted genes, based on comparative analysis of available transcript and genome data from a variety of species. The ASPIC web resource provides graphical and tabular views of the splicing patterns of all full-length mRNA isoforms compatible with the detected splice sites of genes under investigation as well as relevant structural and functional annotation. The ASPIC web resource-available at http://www.caspur.it/ASPIC/--is dynamically interconnected with the Ensembl and Unigene databases and also implements an upload facility.

/pdf/aspic-a-web-resource-for-alternative-splicing-prediction-and-3rs473uel2.pdf

ASPIC: a web resource for alternative splicing prediction and transcript isoforms characterization

Summary: GenoMiner is a software tool that searches for regions of similarity between user-submitted genome or transcript sequences and user-specified whole genome assemblies. The program then identifies conserved sequence tags (CSTs) in these homologous regions and provides a prediction of their coding or non-coding nature. The analysis is carried out through three steps: (1) definition of sequence regions homologous to the query sequence in the selected target genomes by a fast BLAT alignment; (2) identification of CSTs by a more sensitive BLAST-like alignment between the query and the homologous regions in the target genomes and (3) assessment of the coding or non-coding nature of detected CSTs through the computation of a suitable coding potential score. GenoMiner allows the user to search the query sequence against a number of vertebrate genome assemblies in a single run providing a user-friendly graphical output.

Availability: http://www.caspur.it/GenoMiner/. GenoMiner software and documentation is available from the authors upon request.

Contact: graziano.pesole@unimi.it

/pdf/genominer-a-tool-for-genome-wide-search-of-coding-and-non-4wetcw7cau.pdf

Ivano Giuseppe Talamo

Papers

The PMDB Protein Model Database.

ASPIC: a web resource for alternative splicing prediction and transcript isoforms characterization

GenoMiner: a tool for genome-wide search of coding and non-coding conserved sequence tags