nach oben

Translational Stroke Research

Erschienen in:

10.11.2017 | Original Article

Disease of mRNA Regulation: Relevance for Ischemic Brain Injury

verfasst von: Donald J. DeGracia

Erschienen in: Translational Stroke Research | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

Abstract

In this mini-review we give an overview of the role of mRNA-binding proteins and their associated messenger ribonucleoprotein complexes (mRNPs) in several disease states, and bring this information to bear on the pathophysiology of brain ischemia. One conclusion reached is that mRNPs may play a causal role in proteotoxicity instead of being merely passive targets. Ischemia therapies targeting mRNPs have advantages over targeting single pathways, but the behavior of mRNPs needs to be considered in the design of therapies.

Knowles RB, Sabry JH, Martone ME, Deerinck TJ, Ellisman MH, Bassell GJ, et al. Translocation of RNA granules in living neurons. J Neurosci. 1996;16(24):7812–20.CrossRefPubMed

Kedersha N, Anderson P. Regulation of translation by stress granules and processing bodies. Prog Mol Biol Transl Sci. 2009;90:155–85. https://doi.org/10.1016/S1877-1173(09)90004-7.CrossRefPubMed

Kedersha NL, Gupta M, Li W, Miller I, Anderson P. RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules. J Cell Biol. 1999;147(7):1431–42.CrossRefPubMedPubMedCentral

Kedersha N, Tisdale S, Hickman T, Anderson P. Real-time and quantitative imaging of mammalian stress granules and processing bodies. Methods Enzymol. 2008;448:521–52. https://doi.org/10.1016/S0076-6879(08)02626-8.CrossRefPubMed

Aulas A, Fay MM, Szaflarski W, Kedersha N, Anderson P, Ivanov P. Methods to classify cytoplasmic foci as mammalian stress granules. J Vis Exp. 2017;123 https://doi.org/10.3791/55656.

Paz I, Kosti I, Ares M Jr, Cline M, Mandel-Gutfreund Y. RBPmap: a web server for mapping binding sites of RNA-binding proteins. Nucleic Acids Res. 2014;42(Web Server issue):W361–7. https://doi.org/10.1093/nar/gku406.CrossRefPubMedPubMedCentral

Harvey R, Dezi V, Pizzinga M, Willis AE. Post-transcriptional control of gene expression following stress: the role of RNA-binding proteins. Biochem Soc Trans. 2017;45(4):1007–14. https://doi.org/10.1042/BST20160364.CrossRefPubMedPubMedCentral

Simone LE, Keene JD. Mechanisms coordinating ELAV/Hu mRNA regulons. Curr Opin Genet Dev. 2013;23(1):35–43. https://doi.org/10.1016/j.gde.2012.12.006.CrossRefPubMedPubMedCentral

Sajjanar B, Deb R, Raina SK, Pawar S, Brahmane MP, Nirmale AV, et al. Untranslated regions (UTRs) orchestrate translation reprogramming in cellular stress responses. J Therm Biol. 2017;65:69–75. https://doi.org/10.1016/j.jtherbio.2017.02.006.CrossRefPubMed

10.

Bakheet T, Williams BR, Khabar KS. ARED 3.0: the large and diverse AU-rich transcriptome. Nucleic Acids Res. 2006;34(Database issue):D111–4. https://doi.org/10.1093/nar/gkj052.CrossRefPubMed

11.

Fan XC, Steitz JA. Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs. EMBO J. 1998;17(12):3448–60. https://doi.org/10.1093/emboj/17.12.3448.CrossRefPubMedPubMedCentral

12.

Mazan-Mamczarz K, Galban S, Lopez de Silanes I, Martindale JL, Atasoy U, Keene JD, et al. RNA-binding protein HuR enhances p53 translation in response to ultraviolet light irradiation. Proc Natl Acad Sci U S A. 2003;100(14):8354–9. https://doi.org/10.1073/pnas.1432104100.CrossRefPubMedPubMedCentral

13.

Gallouzi IE, Brennan CM, Steitz JA. Protein ligands mediate the CRM1-dependent export of HuR in response to heat shock. RNA. 2001;7(9):1348–61.CrossRefPubMedPubMedCentral

14.

Antic D, Keene JD. Messenger ribonucleoprotein complexes containing human ELAV proteins: interactions with cytoskeleton and translational apparatus. J Cell Sci. 1998;111(Pt 2):183–97.PubMed

15.

Kedersha N, Anderson P. Stress granules: sites of mRNA triage that regulate mRNA stability and translatability. Biochem Soc Trans. 2002;30(Pt 6):963–9. https://doi.org/10.1042/bst0300963.

16.

Gilks N, Kedersha N, Ayodele M, Shen L, Stoecklin G, Dember LM, et al. Stress granule assembly is mediated by prion-like aggregation of TIA-1. Mol Biol Cell. 2004;15(12):5383–98. https://doi.org/10.1091/mbc.E04-08-0715.CrossRefPubMedPubMedCentral

17.

Anderson P, Kedersha N, Ivanov P. Stress granules, P-bodies and cancer. Biochim Biophys Acta. 2015;1849(7):861–70. https://doi.org/10.1016/j.bbagrm.2014.11.009.CrossRefPubMed

18.

Mahboubi H, Stochaj U. Cytoplasmic stress granules: dynamic modulators of cell signaling and disease. Biochim Biophys Acta. 2017;1863(4):884–95. https://doi.org/10.1016/j.bbadis.2016.12.022.CrossRefPubMed

19.

DeGracia DJ. Regulation of mRNA following brain ischemia and reperfusion. Wiley Interdiscip Rev RNA. 2017;8(4). doi:https://doi.org/10.1002/wrna.1415.

20.

Hossmann KA. Disturbances of cerebral protein synthesis and ischemic cell death. Prog Brain Res. 1993;96:161–77.CrossRefPubMed

21.

Kayali F, Montie HL, Rafols JA, DeGracia DJ. Prolonged translation arrest in reperfused hippocampal cornu Ammonis 1 is mediated by stress granules. Neuroscience. 2005;134(4):1223–45. https://doi.org/10.1016/j.neuroscience.2005.05.047.CrossRefPubMed

22.

Jamison JT, Kayali F, Rudolph J, Marshall M, Kimball SR, DeGracia DJ. Persistent redistribution of poly-adenylated mRNAs correlates with translation arrest and cell death following global brain ischemia and reperfusion. Neuroscience. 2008;154(2):504–20. https://doi.org/10.1016/j.neuroscience.2008.03.057.CrossRefPubMedPubMedCentral

23.

DeGracia DJ, Rudolph J, Roberts GG, Rafols JA, Wang J. Convergence of stress granules and protein aggregates in hippocampal cornu ammonis 1 at later reperfusion following global brain ischemia. Neuroscience. 2007;146(2):562–72. https://doi.org/10.1016/j.neuroscience.2007.01.050.CrossRefPubMedPubMedCentral

24.

Hu BR, Martone ME, Jones YZ, Liu CL. Protein aggregation after transient cerebral ischemia. J Neurosci. 2000;20(9):3191–9.CrossRefPubMed

25.

Liu CL, Ge P, Zhang F, Hu BR. Co-translational protein aggregation after transient cerebral ischemia. Neuroscience. 2005;134(4):1273–84. https://doi.org/10.1016/j.neuroscience.2005.05.015.CrossRefPubMedPubMedCentral

26.

Ge P, Luo Y, Liu CL, Hu B. Protein aggregation and proteasome dysfunction after brain ischemia. Stroke. 2007;38(12):3230–6. https://doi.org/10.1161/STROKEAHA.107.487108.CrossRefPubMedPubMedCentral

27.

Truettner JS, Hu K, Liu CL, Dietrich WD, Hu B. Subcellular stress response and induction of molecular chaperones and folding proteins after transient global ischemia in rats. Brain Res. 2009;1249:9–18. https://doi.org/10.1016/j.brainres.2008.10.032.CrossRefPubMed

28.

Ge P, Zhang F, Zhao J, Liu C, Sun L, Hu B. Protein degradation pathways after brain ischemia. Curr Drug Targets. 2012;13(2):159–65.CrossRefPubMed

29.

Ayuso MI, Martinez-Alonso E, Regidor I, Alcazar A. Stress granule induction after brain ischemia is independent of eukaryotic translation initiation factor (eIF) 2alpha phosphorylation and is correlated with a decrease in eIF4B and eIF4E proteins. J Biol Chem. 2016;291(53):27252–64. https://doi.org/10.1074/jbc.M116.738989.CrossRefPubMedPubMedCentral

30.

Jin K, Li W, Nagayama T, He X, Sinor AD, Chang J, et al. Expression of the RNA-binding protein TIAR is increased in neurons after ischemic cerebral injury. J Neurosci Res. 2000;59(6):767–74. https://doi.org/10.1002/(SICI)1097-4547(20000315)59:6<767::AID-JNR9>3.0.CO;2-K.CrossRefPubMed

31.

Jin K, Mao XO, Eshoo MW, Nagayama T, Minami M, Simon RP, et al. Microarray analysis of hippocampal gene expression in global cerebral ischemia. Ann Neurol. 2001;50(1):93–103.CrossRefPubMed

32.

Wang H, Tri Anggraini F, Chen X, DeGracia DJ. Embryonic lethal abnormal vision proteins and adenine and uridine-rich element mRNAs after global cerebral ischemia and reperfusion in the rat. J Cereb Blood Flow Metab : Off J Int Soc Cereb Blood Flow Metab. 2016; https://doi.org/10.1177/0271678X16657572.

33.

Szymanski JJ, Wang H, Jamison JT, DeGracia DJ. HuR function and translational state analysis following global brain ischemia and reperfusion. Transl Stroke Res. 2013;4(6):589–603. https://doi.org/10.1007/s12975-013-0273-2.CrossRefPubMed

34.

Cuadrado A, Navarro-Yubero C, Furneaux H, Kinter J, Sonderegger P, Munoz A. HuD binds to three AU-rich sequences in the 3′-UTR of neuroserpin mRNA and promotes the accumulation of neuroserpin mRNA and protein. Nucleic Acids Res. 2002;30(10):2202–11.CrossRefPubMedPubMedCentral

35.

DeGracia DJ. Acute and persistent protein synthesis inhibition following cerebral reperfusion. J Neurosci Res. 2004;77(6):771–6. https://doi.org/10.1002/jnr.20225.CrossRefPubMed

36.

Ash PE, Vanderweyde TE, Youmans KL, Apicco DJ, Wolozin B. Pathological stress granules in Alzheimer’s disease. Brain Res. 2014;1584:52–8. https://doi.org/10.1016/j.brainres.2014.05.052.CrossRefPubMedPubMedCentral

37.

Wolozin B. Physiological protein aggregation run amuck: stress granules and the genesis of neurodegenerative disease. Discov Med. 2014;17(91):47–52.PubMedPubMedCentral

38.

Gal J, Kuang L, Barnett KR, Zhu BZ, Shissler SC, Korotkov KV, et al. ALS mutant SOD1 interacts with G3BP1 and affects stress granule dynamics. Acta Neuropathol. 2016;132(4):563–76. https://doi.org/10.1007/s00401-016-1601-x.CrossRefPubMedPubMedCentral

39.

Vanderweyde T, Apicco DJ, Youmans-Kidder K, Ash PEA, Cook C, Lummertz da Rocha E, et al. Interaction of tau with the RNA-binding protein TIA1 regulates tau pathophysiology and toxicity. Cell Rep. 2016;15(7):1455–66. https://doi.org/10.1016/j.celrep.2016.04.045.CrossRefPubMedPubMedCentral

40.

Vanderweyde T, Youmans K, Liu-Yesucevitz L, Wolozin B. Role of stress granules and RNA-binding proteins in neurodegeneration: a mini-review. Gerontology. 2013;59(6):524–33. https://doi.org/10.1159/000354170.CrossRefPubMed

41.

Cestra G, Rossi S, Di Salvio M, Cozzolino M. Control of mRNA translation in ALS Proteinopathy. Front Mol Neurosci. 2017;10:85. https://doi.org/10.3389/fnmol.2017.00085.CrossRefPubMedPubMedCentral

42.

BR H, Janelidze S, Ginsberg MD, Busto R, Perez-Pinzon M, Sick TJ, et al. Protein aggregation after focal brain ischemia and reperfusion. J Cereb Blood Flow Metab : Off J Int Soc Cereb Blood Flow Metab. 2001;21(7):865–75. https://doi.org/10.1097/00004647-200107000-00012. CrossRef

43.

Petrov T, Underwood BD, Braun B, Alousi SS, Rafols JA. Upregulation of iNOS expression and phosphorylation of eIF-2alpha are paralleled by suppression of protein synthesis in rat hypothalamus in a closed head trauma model. J Neurotrauma. 2001;18(8):799–812. https://doi.org/10.1089/089771501316919166.CrossRefPubMed

44.

Chou A, Krukowski K, Jopson T, Zhu PJ, Costa-Mattioli M, Walter P, et al. Inhibition of the integrated stress response reverses cognitive deficits after traumatic brain injury. Proc Natl Acad Sci U S A. 2017;114(31):E6420–E6. https://doi.org/10.1073/pnas.1707661114. CrossRefPubMedPubMedCentral

45.

Wiesner D, Tar L, Linkus B, Chandrasekar A, Olde Heuvel F, Dupuis L, et al. Reversible induction of TDP-43 granules in cortical neurons after traumatic injury. Exp Neurol. 2017;299(Pt A):15–25. https://doi.org/10.1016/j.expneurol.2017.09.011.PubMedCrossRef

46.

Kwan T, Floyd CL, Patel J, Mohaimany-Aponte A, King PH. Astrocytic expression of the RNA regulator HuR accentuates spinal cord injury in the acute phase. Neurosci Lett. 2017;651:140–5. https://doi.org/10.1016/j.neulet.2017.05.003.CrossRefPubMed

47.

Beiter T, Hoene M, Prenzler F, Mooren FC, Steinacker JM, Weigert C, et al. Exercise, skeletal muscle and inflammation: ARE-binding proteins as key regulators in inflammatory and adaptive networks. Exerc Immunol Rev. 2015;21:42–57.PubMed

48.

Grammatikakis I, Abdelmohsen K, Gorospe M. Posttranslational control of HuR function. Wiley Interdiscip Rev RNA. 2017;8(1). doi:https://doi.org/10.1002/wrna.1372.

49.

Shang J, Zhao Z. Emerging role of HuR in inflammatory response in kidney diseases. Acta Biochim Biophys Sin Shanghai. 2017;49(9):753–63. https://doi.org/10.1093/abbs/gmx071.CrossRefPubMed

50.

Kwan T, Floyd CL, Kim S, King PH. RNA binding protein human antigen R is translocated in astrocytes following spinal cord injury and promotes the inflammatory response. J Neurotrauma. 2017;34(6):1249–59. https://doi.org/10.1089/neu.2016.4757.CrossRefPubMedPubMedCentral

51.

Wang H, Ding N, Guo J, Xia J, Ruan Y. Dysregulation of TTP and HuR plays an important role in cancers. Tumour Biol. 2016;37(11):14451–61. https://doi.org/10.1007/s13277-016-5397-z.CrossRefPubMed

52.

Fournier MJ, Gareau C, Mazroui R. The chemotherapeutic agent bortezomib induces the formation of stress granules. Cancer Cell Int. 2010;10:12. https://doi.org/10.1186/1475-2867-10-12.CrossRefPubMedPubMedCentral

53.

Moeller BJ, Dewhirst MW. Raising the bar: how HIF-1 helps determine tumor radiosensitivity. Cell Cycle. 2004;3(9):1107–10.CrossRefPubMed

54.

Stoecklin G, Gross B, Ming XF, Moroni C. A novel mechanism of tumor suppression by destabilizing AU-rich growth factor mRNA. Oncogene. 2003;22(23):3554–61. https://doi.org/10.1038/sj.onc.1206418.CrossRefPubMed

55.

Irvine K, Stirling R, Hume D, Kennedy D. Rasputin, more promiscuous than ever: a review of G3BP. Int J Dev Biol. 2004;48(10):1065–77. https://doi.org/10.1387/ijdb.041893ki.CrossRefPubMed

56.

Sharp FR, Kinouchi H, Koistinaho J, Chan PH, Sagar SM. HSP70 heat shock gene regulation during ischemia. Stroke. 1993;24(12 Suppl):I72–5.PubMed

57.

VanGilder RL, Huber JD, Rosen CL, Barr TL. The transcriptome of cerebral ischemia. Brain Res Bull. 2012;88(4):313–9. https://doi.org/10.1016/j.brainresbull.2012.02.002.CrossRefPubMedPubMedCentral

58.

Lloyd RE. Translational control by viral proteinases. Virus Res. 2006;119(1):76–88. https://doi.org/10.1016/j.virusres.2005.10.016.CrossRefPubMed

59.

Yim HC, Williams BR. Protein kinase R and the inflammasome. J Interf Cytokine Res. 2014;34(6):447–54. https://doi.org/10.1089/jir.2014.0008.CrossRef

60.

Dabo S, Meurs EF. dsRNA-dependent protein kinase PKR and its role in stress, signaling and HCV infection. Viruses. 2012;4(11):2598–635. https://doi.org/10.3390/v4112598.CrossRefPubMedPubMedCentral

61.

McCormick C, Khaperskyy DA. Translation inhibition and stress granules in the antiviral immune response. Nat Rev Immunol. 2017;17(10):647–60. https://doi.org/10.1038/nri.2017.63.CrossRefPubMed

62.

Montero H, Trujillo-Alonso V. Stress granules in the viral replication cycle. Viruses. 2011;3(11):2328–38. https://doi.org/10.3390/v3112328.CrossRefPubMedPubMedCentral

63.

O'Collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW. 1,026 experimental treatments in acute stroke. Ann Neurol. 2006;59(3):467–77. https://doi.org/10.1002/ana.20741.CrossRefPubMed

64.

Uversky VN. Intrinsically disordered proteins in overcrowded milieu: membrane-less organelles, phase separation, and intrinsic disorder. Curr Opin Struct Biol. 2017;44:18–30. https://doi.org/10.1016/j.sbi.2016.10.015.CrossRefPubMed

65.

Saarikangas J, Barral Y. Protein aggregation as a mechanism of adaptive cellular responses. Curr Genet. 2016;62(4):711–24. https://doi.org/10.1007/s00294-016-0596-0.CrossRefPubMed

Titel: Disease of mRNA Regulation: Relevance for Ischemic Brain Injury
verfasst von: Donald J. DeGracia
Publikationsdatum: 10.11.2017
Verlag: Springer US
Erschienen in: Translational Stroke Research / Ausgabe 3/2018
Print ISSN: 1868-4483
Elektronische ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-017-0586-7

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Demenzkranke durch Antipsychotika vielfach gefährdet

23.04.2024 Demenz Nachrichten

Wenn Demenzkranke aufgrund von Symptomen wie Agitation oder Aggressivität mit Antipsychotika behandelt werden, sind damit offenbar noch mehr Risiken verbunden als bislang angenommen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2018

The Protein Modification and Degradation Pathways after Brain Ischemia

Correction to: Pre-existing Small Vessel Disease in Patients with Acute Stroke from the Middle East, Southeast Asia, and Philippines

Factors Mediating Outcome After Stroke: Gender, Thrombolysis, and Their Interaction

Uncovering the Rosetta Stone: Report from the First Annual Conference on Key Elements in Translating Stroke Therapeutics from Pre-Clinical to Clinical

Correction to: Inactivation of NSF ATPase Leads to Cathepsin B Release After Transient Cerebral Ischemia