The cellular mechanisms responsible for the cell survival regulation under stress represent a complex and diverse program. Deciphering molecules and pathways involved infine-tuning of cell demise and cyto-protective processes upon stress stimuli is of utmost meaning in biomedicine, since its deregulation is tightly linked to the pathogenesis of numerous diseases, such as pathogen infections, diabetes, neurode-generative diseases and cancer[158]. Actually, recent development clearly demonstrates that our capability to manipulate these endoge-nous survival programs will lead to functional treatment approaches [158].
Notably, the requirements of precise gene regulation during stress response must be achieved at different levels. Considering the impor-tance of RNA processing as critical steps in gene expression, RNA helicases are relevant and potential regulators of cellular stress re-sponses. Indeed, as summarized in this review, these RNA remodeling enzymes have emerged as central players orchestrating the multilayered cellular stress responses. Due to their involvement in lots of regulatory pathways that have direct implications in human health, RNA helicases have gained much attention during the last few years. Mutations in RNA helicases or alterations of their expression levels have been associ-ated with infections, neurological disorders, cancer and aging processes [159,160]. Several RNA helicases are also host factors required for the replication of human pathogenic viruses[46]. Not surprisingly, these en-zymes have been proposed as potential cellular targets for alternative therapies whereas specific inhibitors targeting their catalytic activities have already been developed [161]. According to recent findings outlined here, it is quite evident that RNA helicases are capable of
performing more than one, non-overlapping functions under normal or stress conditions. Nevertheless, there also appear to be a variety of path-ways by which stress-associated RNA helicases can exert their influence.
Undeniably, examples of RNA helicases involved in stress responses will continue to expand. Although identification of RNA helicases intimately associated with stress response program has just emerged, numerous fundamental questions remain unanswered. On the mechanistic side, focused structure–function studies are needed to verify interacting part-ners of RNA helicases. In addition, the study of RNA helicases in authentic RNP complexes and their rearrangement activities during stress re-sponse will probably become central theme. With regard to the cellular function of RNA helicases in stress response, focus will undoubtedly be on identification of specific RNA targets, on elucidating pathways by which environmental stress regulates RNA helicase activity or gene ex-pression, on clarifying means by which these proteins are recruited to their sites of action, and on devising mechanisms by which the physio-logical and biochemical functions of RNA helicases are integrated.
Given that several RNA helicases are reported to undergo posttranslation-al modifications which provide the opportunity to directly link helicase activity with environmental sensing-signal cascades[162], it will be rele-vant to investigate the functional impact of post-translational modi fica-tions on these events.
In this respect, alterations in post-translational modification of RNA helicases could also influence their localization, their associations with partners and their impact on different cellular processes, adding more complexity. Thus a given RNA helicase may have a pro-survival role in some contexts whereas a death-promoting role in others. This context dependence would obviously have paramount implications for the consideration of RNA helicases as possible biomarkers or therapeutic targets. Therefore, the huge spectrum of RNA helicase functions sug-gests the requirement of more than ever a comprehensive understand-ing of its biology before any medical application. Clearly, there is much research to be performed in this area. In a near future, the fast-growing field of molecular designs and RNA technology should yield new in-sights into the regulation exerted by RNA helicases in all aspects of stress responses and survival program.
Acknowledgements
This work isfinancially supported by the National Science Council, Taiwan, Republic of China [grant numbers NSC100-2320-B-009-007-MY3, NSC101-2320-B-009-001-MY3 and NSC102-2911-I-009-101 (to Y.-H.W.L.); grant numbers NSC101-2917-I-564-022, NSC102-2811-B-038-006 and NSC102-2321-B-038-008 (to J.-W.S.)] and the Ministry of Education, Taiwan, Republic of China for a grant of‘Aiming for the Top University Program’ to the National Chiao Tung University.
References
[1]Buchberger A, Bukau B, Sommer T. Protein quality control in the cytosol and the endoplasmic reticulum: brothers in arms. Mol Cell 2010;40:238–52.
[2]Richter K, Haslbeck M, Buchner J. The heat shock response: life on the verge of death. Mol Cell 2010;40:253–66.
[3]Kroemer G, Marino G, Levine B. Autophagy and the integrated stress response. Mol Cell 2010;40:280–93.
[4]Spriggs KA, Bushell M, Willis AE. Translational regulation of gene expression during conditions of cell stress. Mol Cell 2010;40:228–37.
[5]Fulda S, Gorman AM, Hori O, Samali A. Cellular stress responses: cell survival and cell death. Int J Cell Biol 2010;2010:214074.
[6] Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007;35:495–516.
[7]Tabas I, Ron D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol 2011;13:184–90.
[8]He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy.
Annu Rev Genet 2009;43:67–93.
[9]Bialik S, Zalckvar E, Ber Y, Rubinstein AD, Kimchi A. Systems biology analysis of pro-grammed cell death. Trends Biochem Sci 2010;35:556–64.
[10]Ouyang L, Shi Z, Zhao S, et al. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif 2012;45:487–98.
[11]Gonzalez-Polo RA, Boya P, Pauleau AL, et al. The apoptosis/autophagy paradox:
autophagic vacuolization before apoptotic death. J Cell Sci 2005;118:3091–102.
[12]Amelio I, Melino G, Knight RA. Cell death pathology: cross-talk with autophagy and its clinical implications. Biochem Biophys Res Commun 2011;414:277–81.
[13]Pattingre S, Tassa A, Qu X, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 2005;122:927–39.
[14]Vanlangenakker N, Vanden Berghe T, Krysko DV, Festjens N, Vandenabeele P. Mo-lecular mechanisms and pathophysiology of necrotic cell death. Curr Mol Med 2008;8:207–20.
[15]Golstein P, Kroemer G. Cell death by necrosis: towards a molecular definition.
Trends Biochem Sci 2007;32:37–43.
[16]Vanden Berghe T, Linkermann A, Jouan-Lanhouet S, Walczak H, Vandenabeele P.
Regulated necrosis: the expanding network of non-apoptotic cell death pathways.
Nat Rev Mol Cell Biol 2014;15:135–47.
[17] Galluzzi L, Kepp O, Krautwald S, Kroemer G, Linkermann A. Molecular mechanisms of regulated necrosis. Semin Cell Dev Biol 2014.http://dx.doi.org/10.1016/
j.semcdb.2014.02.006(in press).
[18]Miao EA, Rajan JV, Aderem A. Caspase-1-induced pyroptotic cell death. Immunol Rev 2011;243:206–14.
[19]Mocarski ES, Upton JW, Kaiser WJ. Viral infection and the evolution of caspase 8-regulated apoptotic and necrotic death pathways. Nat Rev Immunol 2012;12:79–88.
[20]Fink SL, Cookson BT. Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun 2005;73:1907–16.
[21]Jankowsky E, Gross CH, Shuman S, Pyle AM. Active disruption of an RNA–protein interaction by a DExH/D RNA helicase. Science 2001;291:121–5.
[22]Linder P, Jankowsky E. From unwinding to clamping— the DEAD box RNA helicase family. Nat Rev Mol Cell Biol 2011;12:505–16.
[23]Jankowsky E. RNA helicases at work: binding and rearranging. Trends Biochem Sci 2011;36:19–29.
[24]Rocak S, Linder P. DEAD-box proteins: the driving forces behind RNA metabolism.
Nat Rev Mol Cell Biol 2004;5:232–41.
[25]Fairman-Williams ME, Guenther UP, Jankowsky E. SF1 and SF2 helicases: family matters. Curr Opin Struct Biol 2010;20:313–24.
[26]Singleton MR, Dillingham MS, Wigley DB. Structure and mechanism of helicases and nucleic acid translocases. Annu Rev Biochem 2007;76:23–50.
[27]Donmez I, Patel SS. Mechanisms of a ring shaped helicase. Nucleic Acids Res 2006;34:4216–24.
[28]Rabhi M, Tuma R, Boudvillain M. RNA remodeling by hexameric RNA helicases.
RNA Biol 2010;7:655–66.
[29]Jankowsky E, Fairman ME. RNA helicases—one fold for many functions. Curr Opin Struct Biol 2007;17:316–24.
[30]Pyle AM. Translocation and unwinding mechanisms of RNA and DNA helicases.
Annu Rev Biophys 2008;37:317–36.
[31]Weir JR, Bonneau F, Hentschel J, Conti E. Structural analysis reveals the character-istic features of Mtr4, a DExH helicase involved in nuclear RNA processing and sur-veillance. Proc Natl Acad Sci U S A 2010;107:12139–44.
[32]Fuller-Pace FV. DExD/H box RNA helicases: multifunctional proteins with important roles in transcriptional regulation. Nucleic Acids Res 2006;34:4206–15.
[33]Tanner NK, Linder P. DExD/H box RNA helicases: from generic motors to specific dissociation functions. Mol Cell 2001;8:251–62.
[34]Owttrim GW. RNA helicases: diverse roles in prokaryotic response to abiotic stress.
RNA Biol 2013;10:96–110.
[35]Vashisht AA, Tuteja N. Stress responsive DEAD-box helicases: a new pathway to engineer plant stress tolerance. J Photochem Photobiol B 2006;84:150–60.
[36]Owttrim GW. RNA helicases and abiotic stress. Nucleic Acids Res 2006;34:3220–30.
[37]Medzhitov R, Janeway Jr C. Innate immune recognition: mechanisms and path-ways. Immunol Rev 2000;173:89–97.
[38]Poeck H, Besch R, Maihoefer C, et al. 5′-Triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma. Nat Med 2008;14:1256–63.
[39]Kubler K, Gehrke N, Riemann S, et al. Targeted activation of RNA helicase retinoic acid-inducible gene-I induces proimmunogenic apoptosis of human ovarian cancer cells. Cancer Res 2010;70:5293–304.
[40]Kubler K, tho Pesch C, Gehrke N, et al. Immunogenic cell death of human ovarian cancer cells induced by cytosolic poly(I:C) leads to myeloid cell maturation and ac-tivates NK cells. Eur J Immunol 2011;41:3028–39.
[41]Besch R, Poeck H, Hohenauer T, et al. Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells. J Clin Invest 2009;119:2399–411.
[42]Poeck H, Bscheider M, Gross O, et al. Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production.
Nat Immunol 2010;11:63–9.
[43]Takaoka A, Hayakawa S, Yanai H, et al. Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature 2003;424:516–23.
[44]Lamkanfi M, Dixit VM. Manipulation of host cell death pathways during microbial infections. Cell Host Microbe 2010;8:44–54.
[45]Thompson MR, Kaminski JJ, Kurt-Jones EA, Fitzgerald KA. Pattern recognition receptors and the innate immune response to viral infection. Viruses 2011;3:920–40.
[46]Fullam A, Schroder M. DExD/H-box RNA helicases as mediators of anti-viral innate immunity and essential host factors for viral replication. Biochim Biophys Acta 1829;2013:854–65.
[47]Desmet CJ, Ishii KJ. Nucleic acid sensing at the interface between innate and adap-tive immunity in vaccination. Nat Rev Immunol 2012;12:479–91.
[48]Vabret N, Blander JM. Sensing microbial RNA in the cytosol. Front Immunol 2013;4:468.
[49]Jensen S, Thomsen AR. Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion. J Virol 2012;86:2900–10.
[50]Takahasi K, Kumeta H, Tsuduki N, et al. Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors. J Biol Chem 2009;284:17465–74.
[51]Cui S, Eisenacher K, Kirchhofer A, et al. The C-terminal regulatory domain is the RNA 5′-triphosphate sensor of RIG-I. Mol Cell 2008;29:169–79.
[52]Barbalat R, Ewald SE, Mouchess ML, Barton GM. Nucleic acid recognition by the in-nate immune system. Annu Rev Immunol 2011;29:185–214.
[53]Loo YM, Gale Jr M. Immune signaling by RIG-I-like receptors. Immunity 2011;34:680–92.
[54]Rehwinkel J, Tan CP, Goubau D, et al. RIG-I detects viral genomic RNA during negative-strand RNA virus infection. Cell 2010;140:397–408.
[55]Chiu YH, Macmillan JB, Chen ZJ. RNA polymerase III detects cytosolic DNA and in-duces type I interferons through the RIG-I pathway. Cell 2009;138:576–91.
[56]Ablasser A, Bauernfeind F, Hartmann G, Latz E, Fitzgerald KA, Hornung V. RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat Immunol 2009;10:1065–72.
[57]Kowalinski E, Lunardi T, McCarthy AA, et al. Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA. Cell 2011;147:423–35.
[58]Jiang F, Ramanathan A, Miller MT, et al. Structural basis of RNA recognition and ac-tivation by innate immune receptor RIG-I. Nature 2011;479:423–7.
[59]Zhong B, Yang Y, Li S, et al. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity 2008;29:538–50.
[60]Ishikawa H, Barber GN. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 2008;455:674–8.
[61]Pichlmair A, Schulz O, Tan CP, et al. Activation of MDA5 requires higher-order RNA structures generated during virus infection. J Virol 2009;83:10761–9.
[62]Fredericksen BL, Keller BC, Fornek J, Katze MG, Gale Jr M. Establishment and main-tenance of the innate antiviral response to West Nile Virus involves both RIG-I and MDA5 signaling through IPS-1. J Virol 2008;82:609–16.
[63]Kang DC, Gopalkrishnan RV, Wu Q, Jankowsky E, Pyle AM, Fisher PB. mda-5: an interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties. Proc Natl Acad Sci U S A 2002;99:637–42.
[64]Rothenfusser S, Goutagny N, DiPerna G, et al. The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I. J Immunol 2005;175:5260–8.
[65]Yoneyama M, Kikuchi M, Matsumoto K, et al. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 2005;175:2851–8.
[66]Venkataraman T, Valdes M, Elsby R, et al. Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses. J Immunol 2007;178:6444–55.
[67]Pippig DA, Hellmuth JC, Cui S, et al. The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA. Nucleic Acids Res 2009;37:2014–25.
[68]Ditton HJ, Zimmer J, Kamp C, Rajpert-De Meyts E, Vogt PH. The AZFa gene DBY (DDX3Y) is widely transcribed but the protein is limited to the male germ cells by translation control. Hum Mol Genet 2004;13:2333–41.
[69]Soulat D, Burckstummer T, Westermayer S, et al. The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune re-sponse. EMBO J 2008;27:2135–46.
[70]Schroder M, Baran M, Bowie AG. Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation. EMBO J 2008;27:2147–57.
[71]Gu L, Fullam A, Brennan R, Schroder M. Human DEAD box helicase 3 couples IkappaB kinase epsilon to interferon regulatory factor 3 activation. Mol Cell Biol 2013;33:2004–15.
[72]Oshiumi H, Sakai K, Matsumoto M, Seya T. DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 to up-regulate IFN-beta-inducing potential. Eur J Immunol 2010;40:940–8.
[73]Oshiumi H, Ikeda M, Matsumoto M, et al. Hepatitis C virus core protein abrogates the DDX3 function that enhances IPS-1-mediated IFN-beta induction. PLoS One 2010;5:e14258.
[74]Zhang Z, Yuan B, Bao M, Lu N, Kim T, Liu YJ. The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells. Nat Immunol 2011;12:959–65.
[75]Stein SC, Falck-Pedersen E. Sensing adenovirus infection: activation of interferon regulatory factor 3 in RAW 264.7 cells. J Virol 2012;86:4527–37.
[76]Parvatiyar K, Zhang Z, Teles RM, et al. The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interfer-on immune respinterfer-onse. Nat Immunol 2012;13:1155–61.
[77]Zhang Z, Yuan B, Lu N, Facchinetti V, Liu YJ. DHX9 pairs with IPS-1 to sense double-stranded RNA in myeloid dendritic cells. J Immunol 2011;187:4501–8.
[78]Kim T, Pazhoor S, Bao M, et al. Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells. Proc Natl Acad Sci U S A 2010;107:15181–6.
[79]Zhang Z, Kim T, Bao M, et al. DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells. Immunity 2011;34:866–78.
[80]Miyashita M, Oshiumi H, Matsumoto M, Seya T. DDX60, a DEXD/H box helicase, is a novel antiviral factor promoting RIG-I-like receptor-mediated signaling. Mol Cell Biol 2011;31:3802–19.
[81]Mitoma H, Hanabuchi S, Kim T, et al. The DHX33 RNA helicase senses cytosolic RNA and activates the NLRP3 inflammasome. Immunity 2013;39:123–35.
[82]Liu Y, Lu N, Yuan B, et al. The interaction between the helicase DHX33 and IPS-1 as a novel pathway to sense double-stranded RNA and RNA viruses in myeloid den-dritic cells. Cell Mol Immunol 2014;11:49–57.
[83]Kotwal GJ, Hatch S, Marshall WL. Viral infection: an evolving insight into the signal transduction pathways responsible for the innate immune response. Adv Virol 2012;2012:131457.
[84]Ariumi Y, Kuroki M, Abe K, et al. DDX3 DEAD-box RNA helicase is required for hepatitis C virus RNA replication. J Virol 2007;81:13922–6.
[85]Randall G, Panis M, Cooper JD, et al. Cellular cofactors affecting hepatitis C virus in-fection and replication. Proc Natl Acad Sci U S A 2007;104:12884–9.
[86]Yedavalli VS, Neuveut C, Chi YH, Kleiman L, Jeang KT. Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function. Cell 2004;119:381–92.
[87]Anderson P, Kedersha N. Stress granules: the Tao of RNA triage. Trends Biochem Sci 2008;33:141–50.
[88]Buchan JR, Parker R. Eukaryotic stress granules: the ins and outs of translation. Mol Cell 2009;36:932–41.
[89]Anderson P, Kedersha N. Stress granules. Curr Biol 2009;19:R397–8.
[90]Kedersha N, Anderson P. Stress granules: sites of mRNA triage that regulate mRNA stability and translatability. Biochem Soc Trans 2002;30:963–9.
[91]Thomas MG, Loschi M, Desbats MA, Boccaccio GL. RNA granules: the good, the bad and the ugly. Cell Signal 2011;23:324–34.
[92]Gingras AC, Raught B, Sonenberg N. eIF4 initiation factors: effectors of mRNA re-cruitment to ribosomes and regulators of translation. Annu Rev Biochem 1999;68:913–63.
[93]Kahvejian A, Svitkin YV, Sukarieh R, M'Boutchou MN, Sonenberg N. Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms. Genes Dev 2005;19:104–13.
[94]Imataka H, Gradi A, Sonenberg N. A newly identified N-terminal amino acid se-quence of human eIF4G binds binding protein and functions in poly(A)-dependent translation. EMBO J 1998;17:7480–9.
[95]Anderson P, Kedersha N. RNA granules. J Cell Biol 2006;172:803–8.
[96]Kedersha N, Stoecklin G, Ayodele M, et al. Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. J Cell Biol 2005;169:871–84.
[97]Kedersha N, Ivanov P, Anderson P. Stress granules and cell signaling: more than just a passing phase? Trends Biochem Sci 2013;38:494–506.
[98]Kim WJ, Back SH, Kim V, Ryu I, Jang SK. Sequestration of TRAF2 into stress granules interrupts tumor necrosis factor signaling under stress conditions. Mol Cell Biol 2005;25:2450–62.
[99]Wasserman T, Katsenelson K, Daniliuc S, Hasin T, Choder M, Aronheim A. A novel c-Jun N-terminal kinase (JNK)-binding protein WDR62 is recruited to stress granules and mediates a nonclassical JNK activation. Mol Biol Cell 2010;21:117–30.
[100]Arimoto K, Fukuda H, Imajoh-Ohmi S, Saito H, Takekawa M. Formation of stress granules inhibits apoptosis by suppressing stress-responsive MAPK pathways.
Nat Cell Biol 2008;10:1324–32.
[101]Tsai NP, Wei LN. RhoA/ROCK1 signaling regulates stress granule formation and ap-optosis. Cell Signal 2010;22:668–75.
[102]Thedieck K, Holzwarth B, Prentzell MT, et al. Inhibition of mTORC1 by astrin and stress granules prevents apoptosis in cancer cells. Cell 2013;154:859–74.
[103]Takahashi M, Higuchi M, Matsuki H, et al. Stress granules inhibit apoptosis by re-ducing reactive oxygen species production. Mol Cell Biol 2013;33:815–29.
[104]Gebauer F, Hentze MW. Molecular mechanisms of translational control. Nat Rev Mol Cell Biol 2004;5:827–35.
[105]Holcik M, Sonenberg N. Translational control in stress and apoptosis. Nat Rev Mol Cell Biol 2005;6:318–27.
[106]Spriggs KA, Stoneley M, Bushell M, Willis AE. Re-programming of translation fol-lowing cell stress allows IRES-mediated translation to predominate. Biol Cell 2008;100:27–38.
[107]Hellen CU, Sarnow P. Internal ribosome entry sites in eukaryotic mRNA molecules.
Genes Dev 2001;15:1593–612.
[108]Johannes G, Carter MS, Eisen MB, Brown PO, Sarnow P. Identification of eukaryotic mRNAs that are translated at reduced cap binding complex eIF4F concentrations using a cDNA microarray. Proc Natl Acad Sci U S A 1999;96:13118–23.
[109]Roy B, Vaughn JN, Kim BH, Zhou F, Gilchrist MA, Von Arnim AG. The h subunit of eIF3 promotes reinitiation competence during translation of mRNAs harboring up-stream open reading frames. RNA 2010;16:748–61.
[110]Guil S, Long JC, Caceres JF. hnRNP A1 relocalization to the stress granules reflects a role in the stress response. Mol Cell Biol 2006;26:5744–58.
[111]Fujimura K, Kano F, Murata M. Identification of PCBP2, a facilitator of IRES-mediated translation, as a novel constituent of stress granules and processing bod-ies. RNA 2008;14:425–31.
[112]von Roretz C, Di Marco S, Mazroui R, Gallouzi IE. Turnover of AU-rich-containing mRNAs during stress: a matter of survival. Wiley Interdiscip Rev RNA 2011;2:336–47.
[113]Mazroui R, Di Marco S, Kaufman RJ, Gallouzi IE. Inhibition of the ubiquitin–protea-some system induces stress granule formation. Mol Biol Cell 2007;18:2603–18.
[114]Chen HC, Lin WC, Tsay YG, Lee SC, Chang CJ. An RNA helicase, DDX1, interacting with poly(A) RNA and heterogeneous nuclear ribonucleoprotein K. J Biol Chem 2002;277:40403–9.
[115]Kanai Y, Dohmae N, Hirokawa N. Kinesin transports RNA: isolation and character-ization of an RNA-transporting granule. Neuron 2004;43:513–25.
[116]Onishi H, Kino Y, Morita T, Futai E, Sasagawa N, Ishiura S. MBNL1 associates with YB-1 in cytoplasmic stress granules. J Neurosci Res 2008;86:1994–2002.
[117]Kunde SA, Musante L, Grimme A, et al. The X-chromosome-linked intellectual dis-ability protein PQBP1 is a component of neuronal RNA granules and regulates the appearance of stress granules. Hum Mol Genet 2011;20:4916–31.
[118]Chou CF, Lin WJ, Lin CC, et al. DEAD box protein DDX1 regulates cytoplasmic local-ization of KSRP. PLoS One 2013;8:e73752.
[119]Diaz-Moreno I, Hollingworth D, Frenkiel TA, et al. Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14–3–3 binding. Nat Struct Mol Biol 2009;16:238–46.
[120]Rozen F, Edery I, Meerovitch K, Dever TE, Merrick WC, Sonenberg N. Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F. Mol Cell Biol 1990;10:1134–44.
[121]Low WK, Dang Y, Schneider-Poetsch T, et al. Inhibition of eukaryotic translation ini-tiation by the marine natural product pateamine A. Mol Cell 2005;20:709–22.
[122]Mazroui R, Sukarieh R, Bordeleau ME, et al. Inhibition of ribosome recruitment
[122]Mazroui R, Sukarieh R, Bordeleau ME, et al. Inhibition of ribosome recruitment