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 100-200 nm 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.

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 one 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] Furthermore, many signaling molecules were shown to regulate the formation or dynamics of stress granules; these include the master energy sensor AMP-activated protein kinase (AMPK),[10] the O-GlcNAc transferase enzyme (OGT)[11], and the pro-apoptotic kinase ROCK1.[12]

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.[13]

References

  1. ↑ Kayali F, Montie HL, Rafols JA, DeGracia DJ (2005). "Prolonged translation arrest in reperfused hippocampal cornu Ammonis 1 is mediated by stress granules". Neuroscience 134 (4): 1223–45. doi:10.1016/j.neuroscience.2005.05.047. PMID 16055272.
  2. ↑ Nover L, Scharf KD, Neumann D (Mar 1989). "Cytoplasmic heat shock granules are formed from precursor particles and are associated with a specific set of mRNAs". Mol Cell Biol. 9 (3): 1298–308. PMC 362722. PMID 2725500.
  3. ↑ Paul J. Anderson, Brigham and Women's Hospital
  4. ↑ Forreiter C, Kirschner M, Nover L (Dec 1997). "Stable transformation of an Arabidopsis cell suspension culture with firefly luciferase providing a cellular system for analysis of chaperone activity in vivo". Plant Cell 9 (12): 2171–81. doi:10.1105/tpc.9.12.2171. PMC 157066. PMID 9437862.
  5. ↑ Löw D, Brändle K, Nover L, Forreiter C (Sep 2000). "Cytosolic heat-stress proteins Hsp17.7 class I and Hsp17.3 class II of tomato act as molecular chaperones in vivo". Planta 211 (4): 575–82. doi:10.1007/s004250000315. PMID 11030557.
  6. ↑ Stuger R, Ranostaj S, Materna T, Forreiter C (May 1999). "Messenger RNA-binding properties of nonpolysomal ribonucleoproteins from heat-stressed tomato cells". Plant Physiol. 120 (1): 23–32. doi:10.1104/pp.120.1.23. PMC 59255. PMID 10318680.
  7. ↑ Schmid HP, Akhayat O, Martins De Sa C, Puvion F, Koehler K, Scherrer K (Jan 1984). "The prosome: an ubiquitous morphologically distinct RNP particle associated with repressed mRNPs and containing specific ScRNA and a characteristic set of proteins". EMBO J. 3 (1): 29–34. PMC 557293. PMID 6200323.
  8. ↑ Gilks N, Kedersha N, Ayodele M, et al. (Dec 2004). "Stress granule assembly is mediated by prion-like aggregation of TIA-1". Mol Biol Cell 15 (12): 5383–98. doi:10.1091/mbc.E04-08-0715. PMC 532018. PMID 15371533.
  9. ↑ Ivanov PA, Chudinova EM, Nadezhdina ES (Nov 2003). "Disruption of microtubules inhibits cytoplasmic ribonucleoprotein stress granule formation". Exp. Cell Res. 290 (2): 227–33. doi:10.1016/S0014-4827(03)00290-8. PMID 14567982.
  10. ↑ Mahboubi, Hicham; Barisé, Ramla; Stochaj, Ursula (2015-07-01). "5′-AMP-activated protein kinase alpha regulates stress granule biogenesis". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1853 (7): 1725–1737. doi:10.1016/j.bbamcr.2015.03.015.
  11. ↑ Ohn, Takbum; Kedersha, Nancy; Hickman, Tyler; Tisdale, Sarah; Anderson, Paul. "A functional RNAi screen links O-GlcNAc modification of ribosomal proteins to stress granule and processing body assembly". Nature Cell Biology 10 (10): 1224–1231. doi:10.1038/ncb1783. PMC 4318256. PMID 18794846.
  12. ↑ Tsai, Nien-Pei; Wei, Li-Na (2010-04-01). "RhoA/ROCK1 signaling regulates stress granule formation and apoptosis". Cellular Signalling 22 (4): 668–675. doi:10.1016/j.cellsig.2009.12.001. PMC 2815184. PMID 20004716.
  13. ↑ Kedersha N, Stoecklin G, Ayodele M, et al. (Jun 2005). "Stress granules and processing bodies are dynamically linked sites of mRNP remodeling". J. Cell Biol. 169 (6): 871–84. doi:10.1083/jcb.200502088. PMC 2171635. PMID 15967811.

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