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Alternative splicing (AS) patterns have diverged rapidly during vertebrate evolution, yet the functions of most species- and lineage-specific splicing events are not known. We observe that mammalian-specific AS events are enriched in transcript sequences encoding intrinsically disordered regions (IDRs) of proteins, in particular those containing glycine/tyrosine repeats that mediate formation of higher-order protein assemblies implicated in gene regulation and human disease. These evolutionary changes impact nearly all members of the hnRNP A and D families of RNA binding proteins. Regulation of these events requires formation of unusual, long-range mammalian-specific RNA duplexes. Differential inclusion of the alternative exons controls the formation of tyrosine-dependent multivalent hnRNP assemblies that, in turn, function to globally regulate splicing. Together, our results demonstrate that AS control of IDR-mediated interactions between hnRNPs represents an important and recurring mechanism underlying splicing regulation. Furthermore, this mechanism has expanded the regulatory capacity of mammalian cells.
Pubmed ID: 28709000 RIS Download
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A collection of both commercial and noncommercial software products which includes: Mascot Distiller, Mascot Parser, and Mascot Server. Mascot Distiller is commercial and provides a single interface to process raw data into de-isotoped peak lists. This tool can also be used for the easy distribution of search and quantitative results to colleagues. The non-commercial Mascot Parser software provides an API (Application Programmer Interface) that makes it easier to access search results written in C++, Java, Python and Perl. Mascot Server is non-commercial, and is a collection of peptide mass fingerprints as well as a MS/MS database. A selection of popular sequence databases are available online and include SwissProt, NCBInr, and the EST divisions of EMBL. This server is best used for evaluating and searching for smaller data sets.
View all literature mentionsSoftware integrated tool for conducting automatic and manual sequence alignment, inferring phylogenetic trees, mining web based databases, estimating rates of molecular evolution, and testing evolutionary hypotheses. Used for comparative analysis of DNA and protein sequences to infer molecular evolutionary patterns of genes, genomes, and species over time. MEGA version 4 expands on existing facilities for editing DNA sequence data from autosequencers, mining Web-databases, performing automatic and manual sequence alignment, analyzing sequence alignments to estimate evolutionary distances, inferring phylogenetic trees, and testing evolutionary hypotheses. MEGA version 6 enables inference of timetrees, as it implements RelTime method for estimating divergence times for all branching points in phylogeny.
View all literature mentionsA freely accessible on-line systems biology resource devoted to all aspects of protein modification, as well as other post-translational modifications. It provides valuable and unique tools for both cell biologists and mass spectroscopists. PhosphoSite is a human- and mouse-centric database. It includes features such as: viewing the locations of modified residues on molecular models; browsing and searching MS2 records by disease, tissue, and cell line; submitting lists of peptides to identify previously reported genes; searching by sub-cellular localization, treatment, tissues, cell types, cell lines and diseases, and protein types and protein domains; searching for experimentally-verified kinase substrates and viewing preferred substrate motifs; and viewing MS2 spectra for peptides and sites not previously published.
View all literature mentionsSoftware platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.
View all literature mentionsWeb server for functional enrichment analysis and conversions of gene lists. Web based tool for functional profiling of gene lists from large scale experiments. Has web interface with powerful visualization. Used for analyzing data from any organism.
View all literature mentionsSoftware that enables rapid tool creation by providing a robust, pluggable development framework that simplifies and unifies data file access, and performs standard proteomics and LCMS dataset computations.
View all literature mentionsConsortium to build comprehensive parts list of functional elements in human genome. This includes elements that act at protein and RNA levels, and regulatory elements that control cells and circumstances in which gene is active. Data from 2012-present.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsCollection of genome databases for vertebrates and other eukaryotic species with DNA and protein sequence search capabilities. Used to automatically annotate genome, integrate this annotation with other available biological data and make data publicly available via web. Ensembl tools include BLAST, BLAT, BioMart and the Variant Effect Predictor (VEP) for all supported species.
View all literature mentionsA database of protein families, each represented by multiple sequence alignments and hidden Markov models (HMMs). Users can analyze protein sequences for Pfam matches, view Pfam family annotation and alignments, see groups of related families, look at the domain organization of a protein sequence, find the domains on a PDB structure, and query Pfam by keywords. There are two components to Pfam: Pfam-A and Pfam-B. Pfam-A entries are high quality, manually curated families that may automatically generate a supplement using the ADDA database. These automatically generated entries are called Pfam-B. Although of lower quality, Pfam-B families can be useful for identifying functionally conserved regions when no Pfam-A entries are found. Pfam also generates higher-level groupings of related families, known as clans (collections of Pfam-A entries which are related by similarity of sequence, structure or profile-HMM).
View all literature mentionsPortal to interactively visualize genomic data. Provides reference sequences and working draft assemblies for collection of genomes and access to ENCODE and Neanderthal projects. Includes collection of vertebrate and model organism assemblies and annotations, along with suite of tools for viewing, analyzing and downloading data.
View all literature mentionsWeb application to generate sequence logos, graphical representations of patterns within multiple sequence alignment. Designed to make generation of sequence logos easy. Sequence logo generator.
View all literature mentionsA web server which recognizes tertiary structures from an amino acid sequence based on estimated pairwise energy content. Users can input SWISS-PROT/TrEMBL identifier or accession number, or paste the amino acid sequence.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsSource code of a Cytoscape plugin for functional enrichment visualization. It organizes gene-sets, such as pathways and Gene Ontology terms, into a network to reveal which mutually overlapping gene-sets cluster together.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
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