MSGP: the first database of the protein components of the mammalian stress granules

Abstract

In response to different stress stimuli, cells transiently form stress granules (SGs) in order to protect themselves and re-establish homeostasis. Besides these important cellular functions, SGs are now being implicated in different human diseases, such as neurodegenerative disorders and cancer. SGs are ribonucleoprotein granules, constituted by a variety of different types of proteins, RNAs, factors involved in translation and signaling molecules, being capable of regulating mRNA translation to facilitate stress response. However, until now a complete list of the SG components has not been available. Therefore, we aimer at identifying and linting in an open access database all the proteins described so far as components of SGs. The identification was made through an exhaustive search of studies listed in PubMed and double checked. Moreover, for each identified protein several details were also gathered from public databases, such as the molecular function, the cell types in which they were detected, the type of stress stimuli used to induce SG formation and the reference of the study describing the recruitment of the component to SGs. Expression levels in the context of different neurodegenerative diseases were also obtained and are also described in the database. The Mammalian Stress Granules Proteome is available at https://msgp.pt/ , being a new and unique open access online database, the first to list all the protein components of the SGs identified so far. The database constitutes an important and valuable tool for researchers in this research area of growing interest.

Identification of protein-protected mRNA fragments and structured excised intron RNAs in human plasma by TGIRT-seq peak calling

“…Also prevalent in plasma were RNA fragments containing binding sites for DHX30, a DExH-box RNA helicase; GRWD1, a histone-binding protein that may also play a role in ribosome assembly; ZNF622, a zinc-finger protein; BUD13, a spliceosome component; PPIG, a protein involved in protein-folding; and SERBP1, a mRNA-binding-protein. Notably, seven of these top 15 proteins (DDX3X, DDX6, DHX30, LARP4, SERBP1, SND1, and YBX3) are components of stress granules ( Markmiller et al, 2018 ; Nunes et al, 2019 ).…”

Strategies for Success. Viral Infections and Membraneless Organelles

“…Many proteins involved in SG assembly are RNA binding proteins that favor mRNA stability (TIA-1, TIAR, HuR), mRNA metabolism (G3BP-1, G3BP-2, DDX6, SMN, Staufen1, DHX36, Caprin1, ZBP1, HDAC6, ADAR), signaling proteins (mTOR, RACK1) and interferon-stimulated gene (ISG) products (PKR, ADAR1, RIG-I, RNase L, and OAS (reviewed in Poblete-Durán et al, 2016). Recently, Nunes et al generated an open access electronic resource containing all SGs-recruited protein reported to date (available at https://msgp.pt/) (Nunes et al, 2019). Its assembly is typically a consequence of translation repression upon phosphorylation of the translation initiation factor eIF2α by environmental stress such as heat shock, UV irradiation, oxidative stress, viral infection, and even upon treatment with several drugs (see Table 1).…”

C9orf72-associated SMCR8 protein binds in the ubiquitin pathway and with proteins linked with neurological disease

“…Searching the Mammalian Stress Granules Proteome Database (https://msgp.pt) [102], we found that 18% of the SMCR8 proiein interactome (61/340) and 26% (35/ 201) of the C9orf72 interactome are known SGassociated proteins. It is thus possible that SG components bind endogenous SMCR8-C9orf72 complexes and shepherd them to SGs, although why this would not also be the case for overexpressed exogenous SMCR8 or C9orf72 proteins is unclear.…”