About the database

 

About the MSGP

When faced with cellular stress, eukaryotes respond by activating a series of processes to reestablish cellular homeostasis. From these, the formation of stress granules (SGs) is a conserved strategy among multiple organisms. These granules are directly formed in response to cellular stress and are constituted by proteins, factors essential for translation, signalling molecules and by a variety of different types of RNAs. Although the general composition profile of SGs varies between different cell types and diferent types of stress are observed, all stress granules are constituted by several RNA-binding proteins (RBPs), which are essential to their process of assembly.

 

What are stress granules?

Stress granules are foci of cellular triage during stress,  sequestering mRNAs and proteins, and promoting/silencing the translation of RNA transcripts in order to facilitate the stress response.

 

Why the relevance?

Recently, it was shown that abnormalities in SGs functioning have been associated with pathological changes in several diseases, such as cancer, neurodegenerative diseases, viral infections, autoimmune diseases, diabetes, cerebral ischemia, and even in normal aging. 

The main goal of this catalog is to curate all the proteins described as being part of stress granules in mammalian cells. Moreover, it also identifies different features of stress granules components, and importantly their expression profile in the context of neurodegenerative diseases such as Alzheimer’s, Huntington’s and Parkinson’s diseases.

 

Database features and metodology

All stress granules protein components were curated through the published studies on the theme and available in PubMed. Moreover, for each components different information is listed, namely a description of the protein (Uniprot), the gene entrez ID (Gene database), protein name (Uniprot), chromosomal location (OMIM, Gene database), the connection between the protein and disease (OMIM), molecular function of the protein (Uniprot) and if it is described as an RBP (Uniprot and Castello, A.; Fischer, B.; Eichelbaum, K.; Horos, R.; Beckmann, B.M.; Strein, C.; Davey, N.E.; Humphreys, D.T.; Preiss, T.; Steinmetz, L.M.; Krijgsveld, J.; Hentze, M.W. (2012). Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.  Cell. 149(6):1393-406 ).

To assess the expression profiles of stress granules components in the context of different neurodegenerative diseases, a differential transcriptomic analysis was performed using the GEO2R tool of the GEO Datasets database (https://www.ncbi.nlm.nih.gov/gds). The studies used for this analysis were: GSE33000 (Narayanan M, Huynh JL, Wang K, Yang X et al. Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases. Mol Syst Biol 2014 Jul 30;10:743), GSE28894 and GSE4595 (Lederer CW, Torrisi A, Pantelidou M, Santama N et al. Pathways and genes differentially expressed in the motor cortex of patients with sporadic amyotrophic lateral sclerosis. BMC Genomics 2007 Jan 23;8:26).

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