Stress granule

Stress granules are dense aggregations in the cytosol composed of proteins & RNAs that appear when the cell is under stress. The RNA molecules stored are stalled translation pre-initiation complexes - failed attempts to make protein from mRNA. Stress granules are 100-200nm in size, not surrounded by membrane, and associated with the endoplasmatic reticulum [1]. Note that there are also nuclear stress granules. This article is about the cytosolic variety.

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Proposed functions

The purpose of stress granules might be to protect RNAs from harmful conditions, thus their appearance under stress [2]. The accumulation of RNAs into dense globules could keep them from reacting with harmful chemicals and safe-guard the information coded in their RNA sequence.

Stress granules might also function as a decision point for untranslated mRNAs. Molecules can go down either of three paths: further storage, degradation, or re-initiation of translation [3].

The stress proteins that are the main component of stress granules in plant cells are molecular chaperones that sequester, protect, and possibly repair proteins that unfold during heat and other types of stress [4],[5]. Therefore any association of mRNAs with stress granules may simply be a side effect of the association of partially unfolded RNA-binding proteins with stress granules [6], similar to the association of mRNAs with proteasomes [7].

Formation of stress granules

Environmental stress triggers a series of signals which eventually lead to formation of stress granules. Early on, it involves phosphorylation of eukaryotic translation initiation factor eIF2α. Further downstream, prion-like aggregation of the protein TIA-1 leads to the formation of stress granules. The term prion-like is used because aggregation of TIA-1 is concentration dependent, inhibited by chaperones, and because the aggregates are resistant to proteases [8]. It has also been proposed that microtubules play a role in the formation of stress granules, maybe by transporting granule components. This hypothesis is based on the fact that disruption of microtubules with the chemical nocodazole blocks the appearance of the granules [9].

Connection with processing bodies

Stress granules and processing bodies share RNA and protein components, both appear under stress, and can physically associate with one another. While stress granules are associated with mRNAs, processing bodies are thought to be places of mRNA degradation. It has been proposed that mRNAs selected for degradation are passed from stress granules to processing bodies [10].

• overview of RNA granules, 2006
• molecular details of stress granule assembly & function, 2002
• nuclear stress granules, 2004

Laboratories:

• Anderson lab, post-transcriptional control & inflammatory response
• Zhou lab, neurodegenerative disease
• Morimoto lab, transcriptional regulation & heat shock
• Boccaccio lab, Staufen & stress granules
• Nover lab, stress granules in plants