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Happy Birthday: 30 Years of RNA Helicases

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RNA Remodeling Proteins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2209))

Abstract

RNA helicases are ubiquitous, highly conserved RNA-binding enzymes that use the energy derived from the hydrolysis of nucleoside triphosphate to modify the structure of RNA molecules and/or the functionality of ribonucleoprotein complexes. Ultimately, the action of RNA helicases results in changes in gene expression that allow the cell to perform crucial functions. In this chapter, we review established and emerging concepts for DEAD-box and DExH-box RNA helicases. We mention examples from both eukaryotic and prokaryotic systems, in order to highlight common themes and specific actions.

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References

  1. Linder P, Fuller-Pace F (2015) Happy birthday: 25 years of DEAD-box proteins. Methods Mol Biol 1259:17–33

    Article  CAS  PubMed  Google Scholar 

  2. Linder P, Jankowsky E (2011) From unwinding to clamping—the DEAD box RNA helicase family. Nat Rev Mol Cell Biol 12:505–516

    Article  CAS  PubMed  Google Scholar 

  3. Kossen K, Karginov FV, Uhlenbeck OC (2002) The carboxy-terminal domain of the DExDH protein YxiN is sufficient to confer specificity for 23S rRNA. J Mol Biol 324:625–636

    Article  CAS  PubMed  Google Scholar 

  4. Giraud C, Hausmann S, Lemeille S et al (2015) The C-terminal region of the RNA helicase CshA is required for the interaction with the degradosome and turnover of bulk RNA in the opportunistic pathogen Staphylococcus aureus. RNA Biol 12:658–674

    Article  PubMed  PubMed Central  Google Scholar 

  5. Rogers GW, Komar AA, Merrick WC (2002) eIF4A: the godfather of the DEAD-box helicases. Prog Nucl Acids Res 72:307–331

    Article  CAS  Google Scholar 

  6. Linder P, Lasko PF, Ashburner M et al (1989) Birth of the D-E-A-D box. Nature 337:121–122

    Article  CAS  PubMed  Google Scholar 

  7. Ray BK, Lawson TG, Kramer JC et al (1985) ATP-dependent unwinding of messenger RNA structure by eukaryotic initiation factors. J Biol Chem 260:7651–7658

    CAS  PubMed  Google Scholar 

  8. Sonenberg N (1988) Cap-binding proteins of eukaryotic messenger RNA: functions in initiation and control of translation. Prog Nucleic Acid Res Mol Biol 35:173–207

    Article  CAS  PubMed  Google Scholar 

  9. Rozen F, Edery I, Meerovitch K et al (1990) Bidirectional RNA helicase activity of eukaryotic translation initiation factors 4A and 4F. Mol Cell Biol 10:1134–1144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yang Q, Jankowsky E (2006) The DEAD-box protein Ded1 unwinds RNA duplexes by a mode distinct from translocating helicases. Nat Struct Mol Biol 13:981–986

    Article  CAS  PubMed  Google Scholar 

  11. Sengoku T, Nureki O, Nakamura A et al (2006) Structural basis for RNA unwinding by the DEAD-box protein Drosophila Vasa. Cell 125:287–300

    Article  CAS  PubMed  Google Scholar 

  12. Mallam AL, Del Campo M, Gilman B et al (2012) Structural basis for RNA-duplex recognition and unwinding by the DEAD-box helicase Mss116p. Nature 490:121–125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chen Y, Potratz JP, Tijerina P et al (2008) DEAD-box proteins can completely separate an RNA duplex using a single ATP. Proc Natl Acad Sci U S A 105:20203–20208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu F, Putnam A, Jankowsky E (2008) ATP hydrolysis is required for DEAD-box protein recycling but not for duplex unwinding. Proc Natl Acad Sci U S A 105:20209–20214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fairman M, Maroney PA, Wang W et al (2004) Protein displacement by DExH/D RNA helicases without duplex unwinding. Science 304:730–734

    Article  CAS  PubMed  Google Scholar 

  16. Chamot D, Colvin KR, Kujat-Choy SL et al (2005) RNA structural rearrangement via unwinding and annealing by the cyanobacterial RNA helicase, CrhR. J Biol Chem 280:2036–2044

    Article  CAS  PubMed  Google Scholar 

  17. Ballut L, Marchadier B, Baguet A et al (2005) The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity. Nat Struct Mol Biol 12:861–869

    Article  CAS  PubMed  Google Scholar 

  18. Putnam AA, Jankowsky E (2013) AMP sensing by DEAD-box RNA helicases. J Mol Biol 425:3839–3845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yoneyama M, Kikuchi M, Matsumoto K et al (2005) Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 175:2851–2858

    Article  CAS  PubMed  Google Scholar 

  20. Yoneyama M, Kikuchi M, Natsukawa T et al (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5:730–737

    Article  CAS  PubMed  Google Scholar 

  21. Al-Husini N, Tomares DT, Bitar O et al (2018) Alpha-proteobacterial RNA degradosomes assemble liquid-liquid phase-separated RNP bodies. Mol Cell 71:1027–1039 e1014

    Article  CAS  PubMed  Google Scholar 

  22. Carroll JS, Munchel SE, Weis K (2011) The DExD/H box ATPase Dhh1 functions in translational repression, mRNA decay, and processing body dynamics. J Cell Biol 194:527–537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lee CS, Putnam A, Lu T et al (2020) Recruitment of mRNAs to P granules by condensation with intrinsically-disordered proteins. Elife 9:e52896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hondele M, Sachdev R, Heinrich S et al (2019) DEAD-box ATPases are global regulators of phase-separated organelles. Nature 573:144–148

    Article  CAS  PubMed  Google Scholar 

  25. Redder P, Hausmann S, Khemici V et al (2015) Bacterial versatility requires DEAD-box RNA helicases. FEMS Microbiol Rev 39:392–412

    Article  CAS  PubMed  Google Scholar 

  26. Sokabe M, Fraser CS (2017) A helicase-independent activity of eIF4A in promoting mRNA recruitment to the human ribosome. Proc Natl Acad Sci U S A 114:6304–6309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yourik P, Aitken CE, Zhou F et al (2017) Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity. eLife 6:e31476

    Article  PubMed  PubMed Central  Google Scholar 

  28. Berthelot K, Muldoon M, Rajkowitsch L et al (2004) Dynamics and processivity of 40S ribosome scanning on mRNA in yeast. Mol Microbiol 51:987–1001

    Article  CAS  PubMed  Google Scholar 

  29. Guenther UP, Weinberg DE, Zubradt MM et al (2018) The helicase Ded1p controls use of near-cognate translation initiation codons in 5′ UTRs. Nature 559:130–134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tauber D, Tauber G, Khong A et al (2020) Modulation of RNA condensation by the DEAD-box protein eIF4A. Cell 180:411–426.e416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Redko Y, Aubert S, Stachowicz A et al (2013) A minimal bacterial RNase J-based degradosome is associated with translating ribosomes. Nucleic Acids Res 41:288–301

    Article  CAS  PubMed  Google Scholar 

  32. Khemici V, Poljak L, Luisi BF et al (2008) The RNase E of Escherichia coli is a membrane-binding protein. Mol Microbiol 70:799–813

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Strahl H, Turlan C, Khalid S et al (2015) Membrane recognition and dynamics of the RNA degradosome. PLoS Genet 11:e1004961

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Lehnik-Habrink M, Newman J, Rothe FM et al (2011) RNase Y in Bacillus subtilis: a natively disordered protein that is the functional equivalent of RNase E from Escherichia coli. J Bacteriol 193:5431–5441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Charollais J, Dreyfus M, Iost I (2004) CsdA, a cold-shock RNA helicase from Escherichia coli, is involved in the biogenesis of 50S ribosomal subunit. Nucleic Acids Res 32:2751–2759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Charollais J, Pflieger D, Vinh J et al (2003) The DEAD-box RNA helicase SrmB is involved in the assembly of 50S ribosomal subunits in Escherichia coli. Mol Microbiol 48:1253–1265

    Article  CAS  PubMed  Google Scholar 

  37. Khemici V, Prados J, Petrignani B et al (2020) The DEAD-box RNA helicase CshA is required for fatty acid homeostasis in Staphylococcus aureus. PLoS Genet 16(7):e1008779. https://doi.org/10.1371/journal.pgen.1008779

  38. Saito M, Hess D, Eglinger J et al (2019) Acetylation of intrinsically disordered regions regulates phase separation. Nat Chem Biol 15:51–61

    Article  CAS  PubMed  Google Scholar 

  39. Fuller-Pace FV, Nicol SM, Reid AD et al (1993) DbpA: a DEAD box protein specifically activated by 23S rRNA. EMBO J 12:3619–3626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Nicol SM, Fuller-Pace FV (1995) The “DEAD box” protein DbpA interacts specifically with the peptidyltransferase center in 23S rRNA. Proc Natl Acad Sci U S A 92:11681–11685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Nishi K, Morel-Deville F, Hershey JWB et al (1988) An eIF-4A-like protein is a suppressor of an Escherichia coli mutant defective in 50S ribosomal subunit assembly. Nature 336:496–498

    Article  CAS  PubMed  Google Scholar 

  42. Trubetskoy D, Proux F, Allemand F et al (2009) SrmB, a DEAD-box helicase involved in Escherichia coli ribosome assembly, is specifically targeted to 23S rRNA in vivo. Nucleic Acids Res 37(19):6540–6549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Proux F, Dreyfus M, Iost I (2011) Identification of the sites of action of SrmB, a DEAD-box RNA helicase involved in Escherichia coli ribosome assembly. Mol Microbiol 82:300–311

    Article  CAS  PubMed  Google Scholar 

  44. Iost I, Jain C (2019) A DEAD-box protein regulates ribosome assembly through control of ribosomal protein synthesis. Nucleic Acids Res 47:8193–8206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Rabuck-Gibbons JN, Popova AM, Greene EM et al (2020) SrmB rescues trapped ribosome assembly intermediates. J Mol Biol 432(4):978–990

    Article  CAS  PubMed  Google Scholar 

  46. Shen L, Pelletier J (2020) Selective targeting of the DEAD-box RNA helicase eukaryotic initiation factor (eIF) 4A by natural products. Nat Prod Rep 37:609–616

    Article  CAS  PubMed  Google Scholar 

  47. Novac O, Guenier AS, Pelletier J (2004) Inhibitors of protein synthesis identified by a high throughput multiplexed translation screen. Nucleic Acids Res 32:902–915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Bordeleau ME, Mori A, Oberer M et al (2006) Functional characterization of IRESes by an inhibitor of the RNA helicase eIF4A. Nat Chem Biol 2:213–220

    Article  CAS  PubMed  Google Scholar 

  49. Harigua-Souiai E, Abdelkrim YZ, Bassoumi-Jamoussi I et al (2018) Identification of novel leishmanicidal molecules by virtual and biochemical screenings targeting Leishmania eukaryotic translation initiation factor 4A. PLoS Negl Trop Dis 12:e0006160

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Ozgur S, Buchwald G, Falk S et al (2015) The conformational plasticity of eukaryotic RNA-dependent ATPases. FEBS J 282:850–863

    Article  CAS  PubMed  Google Scholar 

  51. Tanner NK, Linder P (2001) DExD/H box RNA helicases: from generic motors to specific dissociation functions. Mol Cell 8:251–262

    Article  CAS  PubMed  Google Scholar 

  52. Büttner K, Nehring S, Hopfner KP (2007) Structural basis for DNA duplex separation by a superfamily-2 helicase. Nat Struct Biol 14:647–352

    Article  CAS  Google Scholar 

  53. Walbott H, Mouffok S, Capeyrou R et al (2010) Prp43p contains a processive helicase structural architecture with a specific regulatory domain. EMBO J 29:2194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Tauchert MJ, Fourmann JB, Luhrmann R et al (2017) Structural insights into the mechanism of the DEAH-box RNA helicase Prp43. eLife 6:e21510

    Article  PubMed  PubMed Central  Google Scholar 

  55. Aravind L, Koonin EV (1999) G-patch: a new conserved domain in eukaryotic RNA-processing proteins and type D retroviral polyproteins. Trends Biochem Sci 24:342–344

    Article  CAS  PubMed  Google Scholar 

  56. Hausmann S, Geiser J, Vadas O et al (2020) Auxiliary domains of the HrpB bacterial DExH-box helicase shape its RNA preferences. RNA Biol 17(5):637–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Silverman EJ, Maeda A, Wei J et al (2004) Interaction between a G-patch protein and a spliceosomal DEXD/H-box ATPase that is critical for splicing. Mol Cell Biol 24:10101–10110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Christian H, Hofele RV, Urlaub H et al (2014) Insights into the activation of the helicase Prp43 by biochemical studies and structural mass spectrometry. Nucleic Acids Res 42:1162–1179

    Article  CAS  PubMed  Google Scholar 

  59. Last RL, Maddock JR, Woolford JL Jr (1987) Evidence for related functions of the RNA genes of Saccharomyces cerevisiae. Genetics 117:619–631

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Roy J, Kim K, Maddock JR et al (1995) The final stages of spliceosome maturation require Spp2p that can interact with the DEAH box protein Prp2p and promote step 1 of splicing. RNA 1:375–390

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Tsai RT, Fu RH, Yeh FL et al (2005) Spliceosome disassembly catalyzed by Prp43 and its associated components Ntr1 and Ntr2. Genes Dev 19:2991–3003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Tsai RT, Tseng CK, Lee PJ et al (2007) Dynamic interactions of Ntr1-Ntr2 with Prp43 and with U5 govern the recruitment of Prp43 to mediate spliceosome disassembly. Mol Cell Biol 27:8027–8037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Boon KL, Auchynnikava T, Edwalds-Gilbert G et al (2006) Yeast ntr1/spp382 mediates prp43 function in postspliceosomes. Mol Cell Biol 26:6016–6023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Tanaka N, Aronova A, Schwer B (2007) Ntr1 activates the Prp43 helicase to trigger release of lariat-intron from the spliceosome. Genes Dev 21:2312–2325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Guglielmi B, Werner M (2002) The yeast homolog of human PinX1 is involved in rRNA and small nucleolar RNA maturation, not in telomere elongation inhibition. J Biol Chem 277:35712–35719

    Article  CAS  PubMed  Google Scholar 

  66. Lebaron S, Froment C, Fromont-Racine M et al (2005) The splicing ATPase prp43p is a component of multiple preribosomal particles. Mol Cell Biol 25:9269–9282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Boneberg FM, Brandmann T, Kobel L et al (2019) Molecular mechanism of the RNA helicase DHX37 and its activation by UTP14A in ribosome biogenesis. RNA 25:685–701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Colley A, Beggs J, Tollervey D et al (2000) Dhr1p, a putative DEAH-box RNA helicase is associated with the box C+D snoRNA U3. Mol Cell Biol 20:7238–7246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Granneman S, Bernstein KA, Bleichert F et al (2006) Comprehensive mutational analysis of yeast DEXD/H box RNA helicases required for small ribosomal subunit synthesis. Mol Cell Biol 26:1183–1194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sardana R, Liu X, Granneman S et al (2015) The DEAH-box helicase Dhr1 dissociates U3 from the pre-rRNA to promote formation of the central pseudoknot. PLoS Biol 13:e1002083

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Colley A, Beggs JD, Tollervey D et al (2000) Dhr1p, a putative DEAH-box RNA helicase, is associated with the box C+D snoRNP U3. Mol Cell Biol 20:7238–7246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Toroney R, Nielsen KH, Staley JP (2019) Termination of pre-mRNA splicing requires that the ATPase and RNA unwindase Prp43p acts on the catalytic snRNA U6. Genes Dev 33:1555–1574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kim S-H, Smith J, Claude A et al (1992) The purified yeast pre-mRNA splicing factor PRP2 is an RNA-dependent NTPase. EMBO J 11:2319–2326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Chen J-H, Lin R-J (1990) The yeast PRP2 protein, a putative RNA-dependent ATPase, shares extensive sequence homology with two other pre-mRNA splicing factors. Nucleic Acids Res 18:6447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. King DS, Beggs JD (1990) Interactions of PRP2 protein with pre-mRNA splicing complexes in Saccharomyces cerevisiae. Nucleic Acids Res 18:6559–6564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Schwer B, Guthrie C (1991) PRP16 is an RNA-dependent ATPase that interacts transiently with the spliceosome. Nature 349:494–499

    Article  CAS  PubMed  Google Scholar 

  77. Schwer B, Guthrie C (1992) A conformational rearrangement in the spliceosome is dependent on PRP16 and ATP hydrolysis. EMBO J 11:5033–5039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Schwer B, Gross CH (1998) Prp22, a DExH-box RNA helicase, plays two distinct roles in yeast pre-mRNA splicing. EMBO J 17:2086–2094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Schwer B (2008) A conformational rearrangement in the spliceosome sets the stage for Prp22-dependent mRNA release. Mol Cell 30:743–754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Wagner JD, Jankowsky E, Company M et al (1998) The DEAH-box protein PRP22 is an ATPase that mediates ATP-dependent mRNA release from the spliceosome and unwinds RNA duplexes. EMBO J 17:2926–2937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Koo JT, Choe J, Moseley SL (2004) HrpA, a DEAH-box RNA helicase, is involved in mRNA processing of a fimbrial operon in Escherichia coli. Mol Microbiol 52:1813–1826

    Article  CAS  PubMed  Google Scholar 

  82. Salman-Dilgimen A, Hardy PO, Dresser AR et al (2011) HrpA, a DEAH-box RNA helicase, is involved in global gene regulation in the Lyme disease spirochete. PLoS One 6:e22168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Nagata Y, Senbongi J, Ishibashi Y et al (2014) Identification of Burkholderia multivorans ATCC 17616 genetic determinants for fitness in soil by using signature-tagged mutagenesis. Microbiology 160:883–891

    Article  CAS  PubMed  Google Scholar 

  84. Tan H, Zhang L, Weng Y et al (2016) PA3297 counteracts antimicrobial effects of azithromycin in Pseudomonas aeruginosa. Front Microbiol 7:317

    PubMed  PubMed Central  Google Scholar 

  85. Granato LM, Picchi SC, Andrade Mde O et al (2016) The ATP-dependent RNA helicase HrpB plays an important role in motility and biofilm formation in Xanthomonas citri subsp. citri. BMC Microbiol 16:55

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Pietrzyk-Brzezinska AJ, Absmeier E, Klauck E et al (2018) Crystal structure of the Escherichia coli DExH-box NTPase HrpB. Structure 26:1462–1473.e1464

    Article  CAS  PubMed  Google Scholar 

  87. Xin BG, Chen WF, Rety S et al (2018) Crystal structure of Escherichia coli DEAH/RHA helicase HrpB. Biochem Biophys Res Commun 504:334–339

    Article  CAS  PubMed  Google Scholar 

  88. Xu Y, Xu X, Lan R et al (2013) An O Island 172 encoded RNA helicase regulates the motility of Escherichia coli O157:H7. PLoS One 8:e64211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Tanaka N, Schwer B (2006) Mutations in PRP43 that uncouple RNA-dependent NTPase activity and pre-mRNA splicing function. Biochemistry 45:6110–6121

    Google Scholar 

  90. Oyama T, Oka H, Mayanagi K et al (2009) Atomic structures and functional implications of the archaeal RecQ-like helicase Hjm. BMC Struct Biol 9:2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Warrener P, Tamura JK, Collett MS (1993) RNA-stimulated NTPase activity associated with yellow fever virus NS3 protein expressed in bacteria. J Virol 67:989–996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Cordin O, Banroques J, Tanner NK et al (2006) The DEAD-box protein family of RNA helicases. Gene 367:17–37

    Article  CAS  PubMed  Google Scholar 

  93. Jankowsky E (2011) RNA helicases at work: binding and rearranging. Trends Biochem Sci 36:19–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Weir JR, Bonneau F, Hentschel J et al (2010) Structural analysis reveals the characteristic features of Mtr4, a DExH helicase involved in nuclear RNA processing and surveillance. Proc Natl Acad Sci U S A 107:12139–12144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Pang PS, Jankowsky E, Planet PJ et al (2002) The hepatitis C viral NS3 protein is a processive DNA helicase with cofactor enhanced RNA unwinding. EMBO J 21:1168–1176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Pyle AM (2008) Translocation and unwinding mechanisms of RNA and DNA helicases. Annu Rev Biophys 37:317–336

    Article  CAS  PubMed  Google Scholar 

  97. He Y, Andersen GR, Nielsen KH (2010) Structural basis for the function of DEAH helicases. EMBO Rep 11:180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Prabu JR, Muller M, Thomae AW et al (2015) Structure of the RNA helicase MLE reveals the molecular mechanisms for uridine specificity and RNA-ATP coupling. Mol Cell 60:487–499

    Article  CAS  PubMed  Google Scholar 

  99. Jankowsky E, Gross CH, Shuman S et al (2000) The DExH protein NPH-II is a processive and directional motor for unwinding RNA. Nature 403:447–451

    Article  CAS  PubMed  Google Scholar 

  100. Cencic R, Galicia-Vazquez G, Pelletier J (2012) Inhibitors of translation targeting eukaryotic translation initiation factor 4A. Methods Enzymol 511:437–461

    Article  CAS  PubMed  Google Scholar 

  101. Iwasaki S, Floor SN, Ingolia NT (2016) Rocaglates convert DEAD-box protein eIF4A into a sequence-selective translational repressor. Nature 534:558–561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Bordeleau ME, Matthews J, Wojnar JM et al (2005) Stimulation of mammalian translation initiation factor eIF4A activity by a small molecule inhibitor of eukaryotic translation. Proc Natl Acad Sci U S A 102:10460–10465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Low WK, Dang Y, Schneider-Poetsch T et al (2005) Inhibition of eukaryotic translation initiation by the marine natural product pateamine A. Mol Cell 20:709–722

    Article  CAS  PubMed  Google Scholar 

  104. Peters TL, Tillotson J, Yeomans AM et al (2018) Target-based screening against eIF4A1 reveals the marine natural product Elatol as a novel inhibitor of translation initiation with in vivo antitumor activity. Clin Cancer Res 24:4256–4270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Tillotson J, Kedzior M, Guimaraes L et al (2017) ATP-competitive, marine derived natural products that target the DEAD box helicase, eIF4A. Bioorg Med Chem Lett 27:4082–4085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Kim WJ, Kim JH, Jang SK (2007) Anti-inflammatory lipid mediator 15d-PGJ2 inhibits translation through inactivation of eIF4A. EMBO J 26:5020–5032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Jiang C, Tang Y, Ding L et al (2019) Targeting the N terminus of eIF4AI for inhibition of its catalytic recycling. Cell Chem Biol 26(1417–1426):e1415

    Google Scholar 

  108. Muller C, Schulte FW, Lange-Grunweller K et al (2018) Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses. Antivir Res 150:123–129

    Article  PubMed  CAS  Google Scholar 

  109. Hawkins BC, Lindqvist LM, Nhu D et al (2014) Simplified silvestrol analogues with potent cytotoxic activity. ChemMedChem 9:1556–1566

    Article  CAS  PubMed  Google Scholar 

  110. Cencic R, Carrier M, Galicia-Vazquez G et al (2009) Antitumor activity and mechanism of action of the cyclopenta[b]benzofuran, silvestrol. PLoS One 4:e5223

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Abdelkrim YZ, Harigua-Souiai E, Barhoumi M et al (2018) The steroid derivative 6-aminocholestanol inhibits the DEAD-box helicase eIF4A (LieIF4A) from the Trypanosomatid parasite Leishmania by perturbing the RNA and ATP binding sites. Mol Biochem Parasitol 226:9–19

    Article  CAS  PubMed  Google Scholar 

  112. Nakao S, Nogami M, Iwatani M et al (2020) Identification of a selective DDX3X inhibitor with newly developed quantitative high-throughput RNA helicase assays. Biochem Biophys Res Commun 523:795–801

    Article  CAS  PubMed  Google Scholar 

  113. Yang SNY, Atkinson SC, Audsley MD et al (2020) RK-33 is a broad-spectrum antiviral agent that targets DEAD-box RNA helicase DDX3X. Cells 9(1):170

    Article  CAS  PubMed Central  Google Scholar 

  114. Brai A, Ronzini S, Riva V et al (2019) Synthesis and antiviral activity of novel 1,3,4-thiadiazole inhibitors of DDX3X. Molecules 24(21):3988

    Article  CAS  PubMed Central  Google Scholar 

  115. Samal SK, Routray S, Veeramachaneni GK et al (2015) Ketorolac salt is a newly discovered DDX3 inhibitor to treat oral cancer. Sci Rep 5:9982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Maga G, Falchi F, Radi M et al (2011) Toward the discovery of novel anti-HIV drugs. Second-generation inhibitors of the cellular ATPase DDX3 with improved anti-HIV activity: synthesis, structure-activity relationship analysis, cytotoxicity studies, and target validation. ChemMedChem 6:1371–1389

    Article  CAS  PubMed  Google Scholar 

  117. Pandey SC, Jha A, Kumar A et al (2019) Evaluation of antileishmanial potential of computationally screened compounds targeting DEAD-box RNA helicase of Leishmania donovani. Int J Biol Macromol 121:480–487

    Article  CAS  PubMed  Google Scholar 

  118. Iwatani-Yoshihara M, Ito M, Ishibashi Y et al (2017) Discovery and characterization of a eukaryotic initiation factor 4A-3-selective inhibitor that suppresses nonsense-mediated mRNA decay. ACS Chem Biol 12:1760–1768

    Article  CAS  PubMed  Google Scholar 

  119. Yoneyama-Hirozane M, Kondo M, Matsumoto SI et al (2017) High-throughput screening to identify inhibitors of DEAD box helicase DDX41. SLAS Discov 22(9):1084–1092

    CAS  PubMed  Google Scholar 

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Acknowledgments

Work in the author’s laboratory is supported by the Swiss National Science Foundation (MV, 174063; PL, 188736), the Sir Jules Thorn Foundation (MV), the Novartis Foundation for biomedical research (MV, PL), the Ernest Boninchi Foundation (MV, PL) and the Fondation Coromandel (PL).

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  1. Faculty of Medicine, Department of Microbiology and Molecular Medicine, University of Geneva, Genève, Switzerland

    Martina Valentini & Patrick Linder

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  1. Martina Valentini
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  2. Patrick Linder
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Correspondence to Patrick Linder .

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  1. Centre de Biophysique Moléculaire, CNRS UPR4301, Orleans Cedex 2, France

    Marc Boudvillain

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Valentini, M., Linder, P. (2021). Happy Birthday: 30 Years of RNA Helicases. In: Boudvillain, M. (eds) RNA Remodeling Proteins. Methods in Molecular Biology, vol 2209. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0935-4_2

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  • DOI: https://doi.org/10.1007/978-1-0716-0935-4_2

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0934-7

  • Online ISBN: 978-1-0716-0935-4

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