Chemical and CRISPR/Cas9 Tools for Functional Characterization of RNA Helicases

  • Jennifer Chu
  • Jerry Pelletier


RNA helicases are remodeling proteins implicated in all aspects of RNA biology. Several gene expression pathways, such as ribosome biogenesis, splicing, and translation, are mis-regulated in cancer, making the helicases involved in maintaining expression flux through these networks putative drug targets. It is thus important to better understand the normal regulatory constraints of these proteins, as well as develop small molecule tools that can be used to probe their function. CRISPR/Cas9 can make a significant impact by helping to probe RNA helicase function, determining druggability, and linking the biological activity of small molecules to perturbation of RNA helicase activity.


CRISPR/Cas9 Chemical biology RNA helicases Translation Target validation Cancer 


  1. Alachkar H, Santhanam R, Harb JG, Lucas DM, Oaks JJ, Hickey CJ, Pan L, Kinghorn AD, Caligiuri MA, Perrotti D, Byrd JC, Garzon R, Grever MR, Marcucci G (2013) Silvestrol exhibits significant in vivo and in vitro antileukemic activities and inhibits FLT3 and miR-155 expressions in acute myeloid leukemia. J Hemat Oncol 6:21CrossRefGoogle Scholar
  2. Alexandrov A, Colognori D, Steitz JA (2011) Human eIF4AIII interacts with an eIF4G-like partner, NOM1, revealing an evolutionarily conserved function outside the exon junction complex. Genes Dev 25:1078–1090PubMedPubMedCentralCrossRefGoogle Scholar
  3. Ballut L, Marchadier B, Baguet A, Tomasetto C, Séraphin B, Le Hir H (2005) The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity. Nat Struct Mol Biol 12:861–869PubMedCrossRefGoogle Scholar
  4. Barbosa I, Haque N, Fiorini F, Barrandon C, Tomasetto C, Blanchette M, Le Hir H (2012) Human CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon junction complex assembly. Nat Struct Mol Biol 19:983–990PubMedCrossRefGoogle Scholar
  5. Bates GJ, Nicol SM, Wilson BJ, Jacobs AM, Bourdon JC, Wardrop J, Gregory DJ, Lane DP, Perkins ND, Fuller-Pace FV (2005) The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor. EMBO J 24:543–553PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bhat M, Robichaud N, Hulea L, Sonenberg N, Pelletier J, Topisirovic I (2015) Targeting the translation machinery in cancer. Nat Rev Drug Discov 14:261–278PubMedCrossRefGoogle Scholar
  7. Blok LS, Madsen E, Juusola J, Gilissen C, Baralle D, Reijnders MRF, Venselaar H, Helsmoortel C, Cho MT, Hoischen A, Vissers LELM, Koemans TS, Wissink-Lindhout W, Eichler EE, Romano C, Esch HV, Stumpel C, Vreeburg M, Smeets E, Oberndorff K, van Bon BWM, Shaw M, Gecz J, Haan E, Bienek M, Jensen C, Loeys BL, Dijck AV, Innes AM, Racher H, Vermeer S, Donato ND, Rump A, Tatton-Brown K, Parker MJ, Henderson A, Lynch SA, Fryer A, Ross A, Vasudevan P, Kini U, Newbury-Ecob R, Chandler K, Male A, the DDD study, Dijkstra S, Schieving J, Giltay J, van Gassen KLI, Schuurs-Hoeijmakers J, Tan PL, Pediaditakis I, Haas SA, Retterer K, Reed P, Monaghan KG, Haverfield E, Natowicz M, Myers A, Kruer MC, Stein Q, Strauss KA, Brigatti KW, Keating K, Burton BK, Kim KH, Charrow J, Norman J, Foster-Barber A, Kline AD, Kimball A, Zackai E, Harr M, Fox J, McLaughlin J, Lindstrom K, Haude KM, van Roozendaal K, Brunner H, Chung WK, Kooy RF, Pfundt R, Kalscheuer V, Mehta SG, Katsanis N, Kleefstra T (2015) Mutations in DDX3X are a common cause of unexplained intellectual disability with gender-specific effects on Wnt signaling. Am J Hum Genet 97:343–352CrossRefGoogle Scholar
  8. Boesler C, Rigo N, Anokhina MM, Tauchert MJ, Agafonov DE, Kastner B, Urlaub H, Ficner R, Will CL, Lührmann R (2016) A spliceosome intermediate with loosely associated tri-snRNP accumulates in the absence of Prp28 ATPase activity. Nat Commun 7:11997PubMedPubMedCentralCrossRefGoogle Scholar
  9. Bol GM, Vesuna F, Xie M, Zeng J, Aziz K, Gandhi N, Levine A, Irving A, Korz D, Tantravedi S, van Voss MRH, Gabrielson K, Bordt EA, Polster BM, Cope L, van der Groep P, Kondaskar A, Rudek MA, Hosmane RS, van der Wall E, van Diest PJ, Tran PT, Raman V (2015) Targeting DDX3 with a small molecule inhibitor for lung cancer therapy. EMBO Mol Med 7:648–669PubMedPubMedCentralCrossRefGoogle Scholar
  10. Bordeleau ME, Matthews J, Wojnar JM, Lindqvist L, Novac O, Jankowsky E, Sonenberg N, Northcote P, Teesdale-Spittle P, Pelletier J (2005) Stimulation of mammalian translation initiation factor eIF4A activity by a small molecule inhibitor of eukaryotic translation. Proc Natl Acad Sci U S A 102:10460–10465PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bordeleau ME, Robert F, Gerard B, Lindqvist L, Chen SM, Wendel HG, Brem B, Greger H, Lowe SW, Porco JA Jr, Pelletier J (2008) Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model. J Clin Invest 118:2651–2660PubMedPubMedCentralGoogle Scholar
  12. Brai A, Fazi R, Tintori C, Zamperini C, Bugli F, Sanguinetti M, Stigliano E, Esté J, Badia R, Franco S, Martinez MA, Martinez JP, Meyerhans A, Saladini F, Zazzi M, Garbelli A, Maga G, Botta M (2016) Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents. Proc Natl Acad Sci U S A 113:5388–5393PubMedPubMedCentralCrossRefGoogle Scholar
  13. Brandimarte L, Pierini V, Giacomo DD, Borga C, Nozza F, Gorello P, Giordan M, Cazzaniga G, Kronnie G, Starza RL, Mecucci C (2013) New MLLT10 gene recombinations in pediatric T-acute lymphoblastic leukemia. Blood 121:5064–5067PubMedCrossRefGoogle Scholar
  14. Brandimarte L, Starza RL, Gianfelici V, Barba G, Pierini V, Giacomo DD, Cools J, Elia L, Vitale A, Luciano L, Bardi A, Chiaretti S, Matteucci C, Specchia G, Mecucci C (2014) DDX3X-MLLT10 fusion in adults with NOTCH1 positive T-cell acute lymphoblastic leukemia. Haematologica 99:64–66PubMedPubMedCentralCrossRefGoogle Scholar
  15. Budiman ME, Bubenik JL, Miniard AC, Middleton LM, Gerber CA, Cash A, Driscoll DM (2009) Eukaryotic initiation factor 4a3 is a selenium-regulated RNA-binding protein that selectively inhibits selenocysteine incorporation. Mol Cell 35:479–489PubMedPubMedCentralCrossRefGoogle Scholar
  16. Cao S, Sun R, Wang W, Meng X, Zhang Y, Zhang N, Yang S (2017) RNA helicase DHX9 may be a therapeutic target in lung cancer and inhibited by enoxacin. Am J Transl Res 9:674–682PubMedPubMedCentralGoogle Scholar
  17. Causevic M, Hislop RG, Kernohan NM, Carey FA, Kay RA, Steele RJ, Fuller-Pace FV (2001) Overexpression and poly-ubiquitylation of the DEAD-box RNA helicase p68 in colorectal tumours. Oncogene 20:7734–7743PubMedCrossRefGoogle Scholar
  18. Çelik H, Sajwan KP, Selvanathan SP, Marsh BJ, Pai AV, Kont YS, Han J, Minas TZ, Rahim S, Erkizan HV, Toretsky JA, Üren A (2015) Ezrin binds to DEAD-box RNA helicase DDX3 and regulates its function and protein level. Mol Cell Biol 35:3145–3162PubMedPubMedCentralGoogle Scholar
  19. Cencic R, Carrier M, Galicia-Vázquez G, Bordeleau ME, Sukarieh R, Bourdeau A, Brem B, Teodoro JG, Greger H, Tremblay ML, Porco JA Jr, Pelletier J (2009) Antitumor activity and mechanism of action of the cyclopenta[b]benzofuran, silvestrol. PLoS One 4:e5223PubMedPubMedCentralCrossRefGoogle Scholar
  20. Chambers JM, Lindqvist LM, Webb A, Huang DC, Savage GP, Rizzacasa MA (2013) Synthesis of biotinylated episilvestrol: highly selective targeting of the translation factors eIF4AI/II. Org Lett 15:1406–1409PubMedCrossRefGoogle Scholar
  21. Chan CC, Dostie J, Diem MD, Feng W, Mann M, Rappsilber J, Dreyfuss G (2004) eIF4A3 is a novel component of the exon junction complex. RNA 10:200–209PubMedPubMedCentralCrossRefGoogle Scholar
  22. Chen HH, Yu HI, Cho WC, Tarn WY (2015a) DDX3 modulates cell adhesion and motility and cancer cell metastasis via Rac1-mediated signaling pathway. Oncogene 34:2790–2800PubMedCrossRefGoogle Scholar
  23. Chen S, Sanjana NE, Zheng K, Shalem O, Lee K, Shi X, Scott DA, Song J, Pan JQ, Weissleder R, Lee H, Zhang F, Sharp PA (2015b) Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell 160:1246–1260PubMedPubMedCentralCrossRefGoogle Scholar
  24. Chu J, Pelletier J (2015) Targeting the eIF4A RNA helicase as an anti-neoplastic approach. Biochim Biophys Acta 1849:781–791PubMedCrossRefGoogle Scholar
  25. Chu J, Galicia-Vázquez G, Cencic R, Mills JR, Katigbak A, Porco JA Jr, Pelletier J (2016) CRISPR-mediated drug-target validation reveals selective pharmacological inhibition of the RNA helicase, eIF4A. Cell Rep 15:2340–2347PubMedPubMedCentralCrossRefGoogle Scholar
  26. Clark EL, Coulson A, Dalgliesh C, Rajan P, Nicol SM, Fleming S, Heer R, Gaughan L, Leung HY, Elliott DJ, Fuller-Pace FV, Robson CN (2008) The RNA helicase p68 is a novel androgen receptor coactivator involved in splicing and is overexpressed in prostate cancer. Cancer Res 68:7938–7946PubMedPubMedCentralCrossRefGoogle Scholar
  27. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339:819–823PubMedPubMedCentralCrossRefGoogle Scholar
  28. Conroy SC, Dever TE, Owens CL, Merrick WC (1990) Characterization of the 46,000-dalton subunit of eIF-4F. Arch Biochem Biophys 282:363–371PubMedCrossRefGoogle Scholar
  29. Cook D, Brown D, Alexander R, March R, Morgan P, Satterthwaite G, Pangalos MN (2014) Lessons learned from the fate of AstraZeneca’s drug pipeline: a five-dimensional framework. Nat Rev Drug Discov 13:419–431PubMedCrossRefGoogle Scholar
  30. Dardenne E, Pierredon S, Driouch K, Gratadou L, Lacroix-Triki M, Espinoza MP, Zonta E, Germann S, Mortada H, Villemin JP, Dutertre M, Lidereau R, Vagner S, Auboeuf D (2012) Splicing switch of an epigenetic regulator by RNA helicases promotes tumor-cell invasiveness. Nat Struct Mol Biol 19:1139–1146PubMedCrossRefGoogle Scholar
  31. Dardenne E, Polay Espinoza M, Fattet L, Germann S, Lambert MP, Neil H, Zonta E, Mortada H, Gratadou L, Deygas M, Chakrama FZ, Samaan S, Desmet FO, Tranchevent LC, Dutertre M, Rimokh R, Bourgeois CF, Auboeuf D (2014) RNA helicases DDX5 and DDX17 dynamically orchestrate transcription, miRNA, and splicing programs in cell differentiation. Cell Rep 7:1900–1913PubMedCrossRefGoogle Scholar
  32. Dehghani M, Lasko P (2016) C-terminal residues specific to Vasa among DEAD-box helicases are required for its functions in piRNA biogenesis and embryonic patterning. Dev Genes Evol 226:401–412PubMedCrossRefGoogle Scholar
  33. Du C, Li DQ, Li N, Chen L, Li SS, Yang Y, Hou MX, Xie MJ, Zheng ZD (2017) DDX5 promotes gastric cancer cell proliferation in vitro and in vivo through mTOR signaling pathway. Sci Rep 7:42876PubMedPubMedCentralCrossRefGoogle Scholar
  34. Edery I, Hümbelin M, Darveau A, Lee KA, Milburn S, Hershey JW, Trachsel H, Sonenberg N (1983) Involvement of eukaryotic initiation factor 4A in the cap recognition process. J Biol Chem 258:11398–11403PubMedGoogle Scholar
  35. Epling LB, Grace CR, Lowe BR, Partidge JF, Enemark EJ (2015) Cancer-associated mutants of RNA helicase DDX3X are defective in RNA-stimulated ATP hydrolysis. J Mol Biol 427:1779–1796PubMedPubMedCentralCrossRefGoogle Scholar
  36. Erkizan HV, Kong Y, Merchant M, Schlottmann S, Barber-Rotenberg JS, Yuan L, Abaan OD, Chou TH, Dakshanamurthy S, Brown ML, Uren A, Toretsky JA (2009) A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing’s sarcoma. Nat Med 15:750–756PubMedPubMedCentralCrossRefGoogle Scholar
  37. Favaro FP, Alvizi L, Zechi-Ceide RM, Bertola D, Felix TM, de Souza J, Raskin S, Twigg SR, Weiner AM, Armas P, Margarit E, Calcaterra NB, Andersen GR, McGowan SJ, Wilkie AO, Richieri-Costa A, de Almeida ML, Passos-Bueno MR (2014) A noncoding expansion in EIF4A3 causes Richieri-Costa-Pereira syndrome, a craniofacial disorder associated with limb defects. Am J Hum Genets 94:120–128CrossRefGoogle Scholar
  38. Floor SN, Barkovich KJ, Condon KJ, Shokat KM, Doudna JA (2016) Analog sensitive chemical inhibition of the DEAD-box protein DDX3. Protein Sci 25:638–649PubMedCrossRefGoogle Scholar
  39. Fullam A, Schroder M (2013) DExD/H-box RNA helicases as mediators of anti-viral innate immunity and essential host factors for viral replication. Biochim Biophys Acta 1829:854–865PubMedCrossRefGoogle Scholar
  40. Galicia-Vázquez G, Cencic R, Robert F, Agenor AQ, Pelletier J (2012) A cellular response linking eIF4AI activity to eIF4AII transcription. RNA 18:1373–1384PubMedPubMedCentralCrossRefGoogle Scholar
  41. Galicia-Vázquez G, Chu J, Pelletier J (2015) eIF4AII is dispensable for miRNA-mediated gene silencing. RNA 21:1826–1833PubMedPubMedCentralCrossRefGoogle Scholar
  42. Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, Torres SE, Stern-Ginossar N, Brandman O, Whitehead EH, Doudna JA, Lim WA, Weissman JS, Qi LS (2013) CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154:442–451PubMedPubMedCentralCrossRefGoogle Scholar
  43. Grifo JA, Tahara SM, Morgan MA, Shatkin AJ, Merrick WC (1983) New initiation factor activity required for globin mRNA translation. J Biol Chem 258:5804–5810PubMedGoogle Scholar
  44. Guénard F, Labrie Y, Ouellette G, Beauparlant CJ, Durocher F, INHERIT BRCAs (2009) Genetic sequence variations of BRCA1-interacting genes AURKA, BAP1, BARD1 and DHX9 in French Canadian families with high risk of breast cancer. J Hum Genet 54:152–161PubMedCrossRefGoogle Scholar
  45. Han K, Jeng EE, Hess GT, Morgens DW, Li A, Bassik MC (2017) Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nat Biotechnol 35:463–474PubMedPubMedCentralCrossRefGoogle Scholar
  46. Heerma van Voss MR, van Kempen PM, Noorlag R, van Diest PJ, Willems SM, Raman V (2015) DDX3 has divergent roles in head and neck squamous cell carcinomas in smoking versus non-smoking patients. Oral Dis 21:270–271PubMedCrossRefGoogle Scholar
  47. Heerma van Voss MR, Brilliant JD, Vesuna F, Bol GM, van der Wall E, van Diest PJ, Raman V (2017) Combination treatment using DDX3 and PARP inhibitors induces synthetic lethality in BRCA1-proficient breast cancer. Med Oncol 34:33PubMedPubMedCentralCrossRefGoogle Scholar
  48. Hess GT, Frésard L, Han K, Lee CH, Li A, Cimprich KA, Montgomery SB, Bassik MC (2016) Directed evolution using dCas9-targeted somatic hypermutation in mammalian cells. Nat Methods 13:1036–1042PubMedPubMedCentralCrossRefGoogle Scholar
  49. Higa T, Tanaka J, Tsukitani Y, Kikuchi H (1981) Hippuristanols, cytotoxic polyoxygenated steroids from the gorgonian Isis hippuris. Chem Lett 10:1647–1650CrossRefGoogle Scholar
  50. Ito M, Iwatani M, Kamada Y, Sogabe S, Nakao S, Tanaka T, Kawamoto T, Aparicio S, Nakanishi A, Imaeda Y (2017a) Discovery of selective ATP-competitive eIF4A3 inhibitors. Bioorg Med Chem 25:2200–2209PubMedCrossRefGoogle Scholar
  51. Ito M, Tanaka T, Cary DR, Iwatani-Yoshihara M, Kamada Y, Kawamoto T, Aparicio S, Nakanishi A, Imaeda Y (2017b) Discovery of novel 1,4-diacylpiperazines as selective and cell-active eIF4A3 inhibitors. J Med Chem 60:3335–3351PubMedCrossRefGoogle Scholar
  52. Iwasaki S, Floor SN, Ingolia NT (2016) Rocaglates convert DEAD-box protein eIF4A into a sequence-selective translational repressor. Nature 534:558–561PubMedPubMedCentralCrossRefGoogle Scholar
  53. Jankowsky E (2010) RNA helicases. RSC Publishing, LondonCrossRefGoogle Scholar
  54. Jiang L, Gu ZH, Yan ZX, Zhao X, Xie YY, Zhang ZG, Pan CM, Hu Y, cai CP, Dong Y, Huang JY, Wang L, Shen Y, Meng G, Zhou JF, Hu JD, Wang JF, Liu YH, Yang LH, Zhang F, Wang JM, Wang Z, Peng ZG, Chen FY, Sun ZM, Ding H, Shi JM, Hou J, Yan JS, Shi JY, Xu L, Li Y, Lu J, Zheng Z, Xue W, Zhao WL, Chen Z, Chen SJ (2015) Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma. Nat Genet 47:1061–1066PubMedCrossRefGoogle Scholar
  55. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–821PubMedCrossRefGoogle Scholar
  56. Jinek M, East A, Cheng A, Lin S, Ma E, Doudna J (2013) RNA-programmed genome editing in human cells. eLife 2:e00471PubMedPubMedCentralCrossRefGoogle Scholar
  57. Jones DTW, Jäger N, Kool M, Zichner T, Hutter B, Sultan M, Cho YJ, Pugh TJ, Hovestadt V, Stütz AM, Rausch T, Warnatz HJ, Ryzhova M, Bender S, Sturm D, Pleier S, Cin H, Pfaff E, Sieber L, Wittmann A, Remke M, Witt H, Hutter S, Tzaridis T, Weischenfeldt J, Raeder B, Avci M, Amstislavskiy V, Zapatka M, Weber UD, Wang Q, Lastischka B, Bartholomae CCSchmidt M, von Kalle C, Ast V, lawerenz C, Eils J, Kabbe R, Benes V, van Sluis P, Koster J, Volckmann R, Shih D, Betts MJ, Russell RB, Coco S, Tonini GP, Schüller U, Hans V, Graf N, Kim YJ, Monoranu C, Roggendorf W, Unterberg A, Herold-Mende C, Milde T, Kulozik AE, von Deimling A, Witt O, Maass E, Rössler J, Ebinger M, Schuhmann MU, Frühwald MC, Hasselbatt M, Jabado N, Rutkowski S, von Bueren AO, Williamson D, Clifford SC, McCabe MG, Collins VP, Wolf S, Wiemann S, Lehrach H, Brors B, Scheurlen W, Felsberg J, Reifenberger G, Northcott PA, Taylor MD, Meyerson M, Pomeroy SL, Yaspo ML, Korbel JO, Korshunov A, Eils R, Pfister SM, Lichter P (2012) Dissecting the genomic complexity underlying medulloblastoma. Nature 488:100–105PubMedPubMedCentralCrossRefGoogle Scholar
  58. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MDM, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley TJ, Wilson RK, Raphael BJ, Ding L (2013) Mutational landscape and significance across 12 major cancer types. Nature 502:333–339PubMedPubMedCentralCrossRefGoogle Scholar
  59. King ML, Chiang CC, Ling HC, Fujita E, Ochiai M, McPhail AT (1982) X-ray crystal structure of rocaglamide, a novel antileukemic 1H-cyclopenta[b]benzofuran from Aglaia elliptifolia. J Chem Soc Chem Commun 20:1150–1151CrossRefGoogle Scholar
  60. Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR (2016) Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533:420–424PubMedPubMedCentralCrossRefGoogle Scholar
  61. Kondaskar A, Kondaskar S, Fishbein JC, Carter-Cooper BA, Lapidus RG, Sadowska M, Edelman MJ, Hosmane RS (2013) Structure-based drug design and potent anti-cancer activity of tricyclic 5:7:5-fused diimidazo[4,5-d:4′,5′-f][1,3]diazepines. Bioorg Med Chem 21:618–631PubMedCrossRefGoogle Scholar
  62. Kost GC, Yang MY, Li L, Zhang Y, Liu CY, Kim DJ, Ahn CH, Lee YB, Liu ZR (2015) A novel anti-cancer agent, 1-(3,5-dimethoxyphenyl)-4-[(6-fluoro-2-methoxyquinoxalin-3-yl)aminocarbonyl] piperazine (RX-5902), interferes with beta-catenin function through Y593 phospho-p68 RNA helicase. J Cell Biochem 116:1595–1601PubMedCrossRefGoogle Scholar
  63. Kurata M, Rathe SK, Bailey NJ, Aumann NK, Jones JM, Veldhuijzen GW, Moriarity BS, Largaespada DA (2016) Using genome-wide CRISPR library screening with library resistant DCK to find new sources of Ara-C drug resistance in AML. Sci Rep 6:36199PubMedPubMedCentralCrossRefGoogle Scholar
  64. Lai MC, Chang WC, Shieh SY, Tarn WY (2010) DDX3 regulates cell growth through translational control of cyclin E1. Mol Cell Biol 30:5444–5453PubMedPubMedCentralCrossRefGoogle Scholar
  65. Landau DA, Tausch E, Taylor-Weiner AN, Stewart C, Reiter JG, Bahlo J, Kluth S, Bozic I, Lawrence M, Böttcher S, Carter SL, Cibulskis K, Mertens D, Sougnez CL, Rosenberg M, Hess JM, Edelmann J, Kless S, Kneba M, Ritgen M, Fink A, Fischer K, Gabriel S, Lander ES, Nowak MA, Dohner H, Hallek M, Neuberg D, Getz G, Stilgenbauer S, Wu CJ (2015) Mutations driving CLL and their evolution in progression and relapse. Nature 526:525–530PubMedPubMedCentralCrossRefGoogle Scholar
  66. Le Hir H, Saulière J, Wang Z (2016) The exon junction complex as a node of post-transcriptional networks. Nat Rev Mol Cell Biol 17:41–54PubMedCrossRefGoogle Scholar
  67. Lee T, Pelletier J (2016) The biology of DHX9 and its potential as a therapeutic target. Oncotarget 7:42716–42739PubMedPubMedCentralGoogle Scholar
  68. Lee YB, Gong YD, Yoon H, Ahn CH, Jeon MK, Kong JY (2010) Synthesis and anticancer activity of new 1-[(5 or 6-substituted 2-alkoxyquinoxalin-3-yl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives. Bioorg Med Chem 18:7966–7974PubMedCrossRefGoogle Scholar
  69. Lee YB, Gong YD, Kim DJ, Ahn CH, Kong JY, Kang NS (2012) Synthesis, anticancer activity and pharmacokinetic analysis of 1-[(substituted 2-alkoxyquinoxalin-3-yl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives. Bioorg Med Chem 20:1303–1309PubMedCrossRefGoogle Scholar
  70. Lee T, Di Paola D, Malina A, Mills JR, Kreps A, Grosse F, Tang H, Zannis-Hadjopoulos M, Larsson O, Pelletier J (2014) Suppression of the DHX9 helicase induces premature senescence in human diploid fibroblasts in a p53-dependent manner. J Biol Chem 289:22798–22814PubMedPubMedCentralCrossRefGoogle Scholar
  71. Lee T, Paquet M, Larsson O, Pelletier J (2016) Tumor cell survival dependence on the DHX9 DExH-box helicase. Oncogene 35:5093–5105PubMedPubMedCentralCrossRefGoogle Scholar
  72. Li W, Ross-Smith N, Proud CG, Belsham GJ (2001) Cleavage of translation initiation factor 4AI (eIF4AI) but not eIF4AII by foot-and-mouth disease virus 3C protease: identification of the eIF4AI cleavage site. FEBS Lett 507:1–5PubMedCrossRefGoogle Scholar
  73. Lindqvist L, Oberer M, Reibarkh M, Cencic R, Bordeleau ME, Vogt E, Marintchev A, Tanaka J, Fagotto F, Altmann M, Wagner G, Pelletier J (2008) Selective pharmacological targeting of a DEAD box RNA helicase. PLoS One 3:e1583PubMedPubMedCentralCrossRefGoogle Scholar
  74. Liu ZR (2002) p68 RNA helicase is an essential human splicing factor that acts at the U1 snRNA-5′ splice site duplex. Mol Cell Biol 22:5443–5450PubMedPubMedCentralCrossRefGoogle Scholar
  75. Liu Y, Lu N, Yuan B, Weng L, Wang F, Liu YJ, Zhang Z (2014) The interaction between the helicase DHX33 and IPS-1 as a novel pathway to sense double-stranded RNA and RNA viruses in myeloid dendritic cells. Cell Mol Immunol 11:49–57PubMedCrossRefGoogle Scholar
  76. Lopez MS, Kliegman JI, Shokat KM (2014) The logic and design of analog-sensitive kinases and their small molecule inhibitors. Methods Enzymol 548:189–213PubMedCrossRefGoogle Scholar
  77. Low WK, Dang Y, Schneider-Poetsch T, Shi Z, Choi NS, Merrick WC, Romo D, Liu JO (2005) Inhibition of eukaryotic translation initiation by the marine natural product pateamine A. Mol Cell 20:709–722PubMedCrossRefGoogle Scholar
  78. Lucas DM, Edwards RB, Lozanski G, West DA, Shin JD, Vargo MA, Davis ME, Rozewski DM, Johnson AJ, Su BN, Goettl VM, Heerema NA, Lin TS, Lehman A, Zhang X, Jarjoura D, Newman DJ, Byrd JC, Kinghorn AD, Grever MR (2009) The novel plant-derived agent silvestrol has B-cell selective activity in chronic lymphocytic leukemia and acute lymphoblastic leukemia in vitro and in vivo. Blood 113:4656–4666PubMedPubMedCentralCrossRefGoogle Scholar
  79. Ma Y, Zhang J, Yin W, Zhang Z, Song Y, Chang X (2016) Targeted AID-mediated mutagenesis (TAM) enables efficient genomic diversification in mammalian cells. Nat Methods 13:1029–1035PubMedCrossRefGoogle Scholar
  80. Maga G, Falchi F, Garbelli A, Belfiore A, Witvrouw M, Manetti F, Botta M (2008) Pharmacophore modeling and molecular docking led to the discovery of inhibitors of human immunodeficiency virus-1 replication targeting the human cellular aspartic acid-glutamic acid-alanine-aspartic acid box polypeptide 3. J Med Chem 51:6635–6638PubMedCrossRefGoogle Scholar
  81. Maga G, Falchi F, Radi M, Botta L, Casaluce G, Bernardini M, Irannejad H, Manetti F, Garbelli A, Samuele Z, Zanoli S, Esté JA, Gonzalez E, Zucca E, Paolucci S, Baldanti F, De Rijck J, Debyser Z, Botta M (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 6:1371–1389PubMedCrossRefGoogle Scholar
  82. Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM (2013) RNA-guided human genome engineering via Cas9. Science 339:823–826PubMedPubMedCentralCrossRefGoogle Scholar
  83. Malina A, Mills JR, Cencic R, Yan Y, Fraser J, Schippers LM, Paquet M, Dostie J, Pelletier J (2013) Repurposing CRISPR/Cas9 for in situ functional assays. Genes Dev 27:2602–2614PubMedPubMedCentralCrossRefGoogle Scholar
  84. Mao H, McMahon JJ, Tsai YH, Wang Z, Silver DL (2016) Haploinsufficiency for core exon junction complex components disrupts embryonic neurogenesis and causes p53-mediated microcephaly. PLoS Genet 12:e1006282PubMedPubMedCentralCrossRefGoogle Scholar
  85. Mastrangelo E, Pezzullo M, De Burghgraeve T, Kaptein S, Pastrino B, Dallmeier K, de Lamballerie X, Neyts J, Hanson AM, Frick DN, Bolognesi M, Milani M (2012) Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug. J Antimicrob Chemother 67:1884–1894PubMedPubMedCentralCrossRefGoogle Scholar
  86. May WA, Gishizky ML, Lessnick SL, Lunsford LB, Lewis BC, Delattre O, Zucman J, Thomas G, Denny CT (1993a) Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation. Proc Natl Acad Sci U S A 90:5752–5756PubMedPubMedCentralCrossRefGoogle Scholar
  87. May WA, Lessnick SL, Braun BS, Klemsz M, Lewis BC, Lunsford LB, Hromas R, Denny CT (1993b) The Ewing’s sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1. Mol Cell Biol 13:7393–7398PubMedPubMedCentralCrossRefGoogle Scholar
  88. Meijer HA, Kong YW, Lu WT, Wilczynska A, Spriggs RV, Robinson SW, Godfrey JD, Willis AE, Bushell M (2013) Translational repression and eIF4A2 activity are critical for microRNA-mediated gene regulation. Science 340:82–85PubMedCrossRefGoogle Scholar
  89. Miao X, Yang ZL, Xiong L, Zou Q, Yuan Y, Li J, Liang L, Chen M, Chen S (2013) Nectin-2 and DDX3 are biomarkers for metastasis and poor prognosis of squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder. Int J Clin Exp Pathol 6:179–190PubMedPubMedCentralGoogle Scholar
  90. Miller EE, Kobayashi GS, Musso CM, Allen M, Ishiy FAA, de Caires LC Jr, Goulart E, Griesi-Oliveira K, Zechi-Ceide RM, Richieri-Costa A, Bertola DR, Passos-Bueno MR, Silver DL (2017) EIF4A3 deficient human iPSCs and mouse models demonstrate neural crest defects that underlie Richieri-Costa-Pereira syndrome. Hum Mol Genet 26:2177–2191PubMedCrossRefGoogle Scholar
  91. Mills JR, Malina A, Lee T, Di Paola D, Larsson O, Miething C, Grosse F, Tang H, Zannis-Hadjopoulos M, Lowe SW, Pelletier J (2013) RNAi screening uncovers Dhx9 as a modifier of ABT-737 resistance in an Emu-myc/Bcl-2 mouse model. Blood 121:3402–3412PubMedPubMedCentralCrossRefGoogle Scholar
  92. Mitoma H, Hanabuchi S, Kim T, Bao M, Zhang Z, Sugimoto N, Liu YJ (2013) The DHX33 RNA helicase senses cytosolic RNA and activates the NLRP3 inflammasome. Immunity 39:123–135PubMedPubMedCentralCrossRefGoogle Scholar
  93. Nguyen LS, Kim HG, Rosenfeld JA, Shen Y, Gusella JF, Lacassie Y, Layman LC, Shaffer LG, Gécz J (2013) Contribution of copy number variants involving nonsense-mediated mRNA decay pathway genes to neuro-developmental disorders. Hum Mol Genet 22:1816–1825PubMedCrossRefGoogle Scholar
  94. Nielsen PJ, McMaster GK, Trachsel H (1985) Cloning of eukaryotic protein synthesis initiation factor genes: isolation and characterization of cDNA clones encoding factor eIF-4A. Nucleic Acids Res 13:6867–6880PubMedPubMedCentralCrossRefGoogle Scholar
  95. Nielsen KH, Chamieh H, Andersen CB, Fredslund F, Hamborg K, Le Hir H, Andersen GR (2009) Mechanism of ATP turnover inhibition in the EJC. RNA 15:67–75PubMedPubMedCentralCrossRefGoogle Scholar
  96. Northcote PT, Blunt JW, Munro MHG (1991) Pateamine – a potent cytotoxin from the New-Zealand marine sponge, Mycale Sp. Tetrahedron Lett 32:6411–6414CrossRefGoogle Scholar
  97. Ojha J, Secreto CR, Rabe KG, Van Dyke DL, Kortum KM, Slager SL, Shanafelt TD, Fonseca R, Kay NE, Braggio E (2015) Identification of recurrent truncated DDX3X mutations in chronic lymphocytic leukaemia. Br J Haematol 169:445–448PubMedCrossRefGoogle Scholar
  98. Palacios IM, Gatfield D, St Johnston D, Izaurralde E (2004) An eIF4AIII-containing complex required for mRNA localization and nonsense-mediated mRNA decay. Nature 427:753–757PubMedCrossRefGoogle Scholar
  99. Pugh TJ, Weeraratne SD, Archer TC, Krummel DAP, Auclair D, Bochicchio J, Careiro MO, Carter SL, Cibulskis K, Erlich RL, Greulich H, Lawrence MS, Lennon NJ, McKenna A, Meldrim J, Ramos AH, Ross MG, Russ C, Shefler E, Sivachenko A, Sogoloff B, Stojanov P, Tamayo P, Mesirov JP, Amani V, Teider N, Sengupta S, Francois JP, Northcott PA, Taylor MD, Yu F, Crabtree GR, Kautzman AG, Gabriel SB, Getz G, Jäger N, Jones DTW, Lichter P, Pfister SM, Roberts TM, Meyerson M, Pomeroy SL, Cho YJ (2012) Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 488:106–110PubMedPubMedCentralCrossRefGoogle Scholar
  100. Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS, Arkin AP, Lim WA (2013) Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell 152:1173–1183PubMedPubMedCentralCrossRefGoogle Scholar
  101. Radi M, Falchi F, Garbelli A, Samuele A, Bernardo V, Paolucci S, Baldanti F, Schenone S, Manetti F, Maga G, Botta M (2012) Discovery of the first small molecule inhibitor of human DDX3 specifically designed to target the RNA binding site: towards the next generation HIV-1 inhibitors. Bioorg Med Chem Lett 22:2094–2098PubMedCrossRefGoogle Scholar
  102. Robinson G, Parker M, Kranenburg TA, Lu C, Chen X, Ding L, Phoenix TN, Hedlund E, Wei L, Zhu X, Chalhoub N, Baker SJ, Huether R, Kriwacki R, Curley N, Thiruvenkatam R, Wang J, Wu G, Rusch M, Hong X, Becksfort J, Gupta P, Ma J, Easton J, Vadodaria B, Onar-Thomas A, Lin T, Li S, Pounds S, Paugh S, Zhao D, Kawauchi D, Roussel MF, Finkelstein D, Ellison DW, Lau CC, Bouffet E, Hassall T, Gururangana S, Cohn R, Fulton RS, Fulton LL, Dooling DJ, Ochoa K, Gajjar A, Mardis ER, Wilson RK, Downing JR, Zhang J, Gilbertson RJ (2012) Novel mutations target distinct subgroups of medulloblastoma. Nature 488:43–48PubMedPubMedCentralCrossRefGoogle Scholar
  103. Rossow KL, Janknecht R (2003) Synergism between p68 RNA helicase and the transcriptional coactivators CBP and p300. Oncogene 22:151–156PubMedCrossRefGoogle Scholar
  104. Sadlish H, Galicia-Vazquez G, Paris CG, Aust T, Bhullar B, Chang L, Helliwell SB, Hoepfner D, Knapp B, Riedl R, Roggo S, Schuierer S, Studer C, Porco JA Jr, Pelletier J, Movva NR (2013) Evidence for a functionally relevant rocaglamide binding site on the eIF4A-RNA complex. ACS Chem Biol 8:1519–1527PubMedPubMedCentralCrossRefGoogle Scholar
  105. Santagata S, Mendillo ML, Tang YC, Subramanian A, Perley CC, Roche SP, Wong B, Narayan R, Kwon H, Koeva M, Amon A, Golub TR, Porco JA Jr, Whitesell L, Lindquist S (2013) Tight coordination of protein translation and HSF1 activation supports the anabolic malignant state. Science 341:1238303PubMedPubMedCentralCrossRefGoogle Scholar
  106. Saporita AJ, Chang HC, Winkeler CL, Apicelli AJ, Kladney RD, Wang J, Townsend RR, Michel LS, Weber JD (2011) RNA helicase DDX5 is a p53-independent target of ARF that participates in ribosome biogenesis. Cancer Res 71:6708–6717PubMedPubMedCentralCrossRefGoogle Scholar
  107. Sarkar M, Khare V, Guturi KK, Das N, Ghosh MK (2015) The DEAD box protein p68: a crucial regulator of AKT/FOXO3a signaling axis in oncogenesis. Oncogene 34:5843–5856PubMedCrossRefGoogle Scholar
  108. Saulière J, Murigneux V, Wang Z, Marquenet E, Barbosa I, Le Tonquèze O, Audic Y, Paillard L, Roest Crollius H, Le Hir H (2012) CLIP-seq of eIF4AIII reveals transcriptome-wide mapping of the human exon junction complex. Nat Struct Mol Biol 19:1124–1131PubMedCrossRefGoogle Scholar
  109. Sharma D, Jankowsky E (2014) The Ded1/DDX3 subfamily of DEAD-box RNA helicases. Crit Rev Biochem Mol Biol 49:343–360PubMedCrossRefGoogle Scholar
  110. Shibuya T, Tango TØ, Sonenberg N, Moore MJ (2004) eIF4AIII binds spliced mRNA in the exon junction complex and is essential for nonsense-mediated decay. Nat Struct Mol Biol 11:346–351PubMedCrossRefGoogle Scholar
  111. Shibuya T, Tango TØ, Stroupe ME, Moore MJ (2006) Mutational analysis of human eIF4AIII identifies regions necessary for exon junction complex formation and nonsense-mediated mRNA decay. RNA 12:360–374PubMedPubMedCentralCrossRefGoogle Scholar
  112. Shin S, Rossow KL, Grande JP, Janknecht R (2007) Involvement of RNA helicases p68 and p72 in colon cancer. Cancer Res 67:7572–7578PubMedCrossRefGoogle Scholar
  113. Steckelberg AL, Boehm V, Gromadzka AM, Gehring NH (2012) CWC22 connects pre-mRNA splicing and exon junction complex assembly. Cell Rep 2:454–461PubMedCrossRefGoogle Scholar
  114. Stevenson RJ, Hamilton SJ, MacCallum DE, Hall PA, Fuller-Pace FV (1998) Expression of the ‘dead box’ RNA helicase p68 is developmentally and growth regulated and correlates with organ differentiation/maturation in the fetus. J Pathol 184:351–359PubMedCrossRefGoogle Scholar
  115. Story RM, Weber IT, Steitz TA (1992) The structure of the E. coli recA protein monomer and polymer. Nature 355:318–325PubMedCrossRefGoogle Scholar
  116. Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A, Shefler E, Ramos AH, Stojanov P, Carter SL, Voet D, Cortés ML, Auclair D, Berger MF, Saksena G, Guiducci C, Onofrio RC, Parkin M, Romkes M, Weissfeld JL, Seethala RR, Wang L, Rangel-Escareño C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Winckler W, Ardlie K, Gabriel SB, Meyerson M, Lander ES, Getz G, Golub TR, Garraway LA, Grandis JR (2011) The mutational landscape of head and neck squamous cell carcinoma. Science 333:1157–1160PubMedPubMedCentralCrossRefGoogle Scholar
  117. Sun Z, Wang L, Eckloff BW, Deng B, Wang Y, Wampfler JA, Jang J, Wieben ED, Jen J, You M, Yang P (2014) Conserved recurrent gene mutations correlate with pathway deregulation and clinical outcomes of lung adenocarcinoma in never-smokers. BMC Med Genet 7:32Google Scholar
  118. Suzuki HI, Yamagata K, Sugimoto K, Iwamoto T, Kato S, Miyazono K (2009) Modulation of microRNA processing by p53. Nature 460:529–533PubMedCrossRefGoogle Scholar
  119. Teigelkamp S, Mundt C, Achsel T, Will CL, Lührmann R (1997) The human U5 snRNP-specific 100-kD protein is an RS domain-containing, putative RNA helicase with significant homology to the yeast splicing factor Prp28p. RNA 3:1313–1326PubMedPubMedCentralGoogle Scholar
  120. Thomas A, Goumans H, Amesz H, Benne R, Voorma HO (1979) A comparison of the initiation factors of eukaryotic protein synthesis from ribosomes and from the postribosomal supernatant. Eur J Biochem 98:329–337PubMedCrossRefGoogle Scholar
  121. Toretsky JA, Erkizan V, Levenson A, Abaan OD, Parvin JD, Cripe TP, Rice AM, Lee SB, Uren A (2006) Oncoprotein EWS-FLI1 activity is enhanced by RNA helicase A. Cancer Res 66:5574–5581PubMedCrossRefGoogle Scholar
  122. Valentin-Vega YA, Wang YD, Parker M, Patmore DM, Kanagaraj A, Moore J, Rusch M, Finkelstein D, Ellison DW, Gilbertson RJ, Zhang J, Kim HJ, Taylor P (2016) Cancer-associated DDX3X mutations drive stress granule assembly and impair global translation. Sci Rep 6:25996PubMedPubMedCentralCrossRefGoogle Scholar
  123. Vojta A, Dobrinić P, Tadić V, Bočkor L, Korać P, Julg B, Klasić M, Zoldoš V (2016) Repurposing the CRISPR-Cas9 system for targeted DNA methylation. Nucleic Acids Res 44:5615–5628PubMedPubMedCentralCrossRefGoogle Scholar
  124. Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K, Werner L, Sivachenko A, DeLuca DS, Zhang L, Zhang W, Vartanov AR, Fernandes SM, Goldstein NR, Folco EG, Cibulskis K, Tesar B, Sievers QL, Shefler E, Gabriel S, Hacohen N, Reed R, Meyerson M, Golub TR, Lander ES, Neuberg D, Brown JR, Getz G, Wu CJ (2011) SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 365:2497–2506PubMedPubMedCentralCrossRefGoogle Scholar
  125. Wang D, Huang J, Hu Z (2012a) RNA helicase DDX5 regulates microRNA expression and contributes to cytoskeletal reorganization in basal breast cancer cells. Mol Cell Proteomics 11:M111.011932PubMedCrossRefGoogle Scholar
  126. Wang R, Jiao Z, Li R, Yue H, Chen L (2012b) p68 RNA helicase promotes glioma cell proliferation in vitro and in vivo via direct regulation of NF-kappaB transcription factor p50. Neuro-Oncology 14:1116–1124PubMedPubMedCentralCrossRefGoogle Scholar
  127. Wang H, Gao X, Yang JJ, Liu ZR (2013) Interaction between p68 RNA helicase and Ca2+-calmodulin promotes cell migration and metastasis. Nat Commun 4:1354PubMedPubMedCentralCrossRefGoogle Scholar
  128. Wang Z, Murigneux V, Le Hir H (2014) Transcriptome-wide modulation of splicing by the exon junction complex. Genome Biol 15:551PubMedPubMedCentralCrossRefGoogle Scholar
  129. Wang T, Birsoy K, Hughes NW, Krupczak KM, Post Y, Wei JJ, Lander ES, Sabatini DM (2015) Identification and characterization of essential genes in the human genome. Science 350:1096–1101PubMedPubMedCentralCrossRefGoogle Scholar
  130. Wilson BJ, Bates GJ, Nicol SM, Gregory DJ, Perkins ND, Fuller-Pace FV (2004) The p68 and p72 DEAD box RNA helicases interact with HDAC1 and repress transcription in a promoter-specific manner. BMC Mol Biol 5:11PubMedPubMedCentralCrossRefGoogle Scholar
  131. Wolfe AL, Singh K, Zhong Y, Drewe P, Rajasekhar VK, Sanghvi VR, Mavrakis KJ, Jiang M, Roderick JE, Van der Meulen J, Schatz JH, Rodrigo CM, Zhao C, Rondou P, de Stanchina E, Teruya-Feldstein J, Kelliher MA, Speleman F, Porco JA Jr, Pelletier J, Rätsch G, Wendel HG (2014) RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer. Nature 513:65–70PubMedPubMedCentralCrossRefGoogle Scholar
  132. Xie M, Vesuna F, Botlagunta M, Bol GM, Irving A, Bergman Y, Hosmane RS, Kato Y, Winnard PT Jr, Raman V (2015) NZ51, a ring-expanded nucleoside analog, inhibits motility and viability of breast cancer cells by targeting the RNA helicase DDX3. Oncotarget 6:29901–29913PubMedPubMedCentralGoogle Scholar
  133. Xie M, Vesuna F, Tantravedi S, Bol GM, Heerma van Voss MR, Nugent K, Malek R, Gabrielson K, van Diest PJ, Tran PT, Raman V (2016) RK-33 Radiosensitizes prostate cancer cells by blocking the RNA helicase DDX3. Cancer Res 76:6340–6350PubMedPubMedCentralCrossRefGoogle Scholar
  134. Yang L, Lin C, Liu ZR (2006) P68 RNA helicase mediates PDGF-induced epithelial mesenchymal transition by displacing Axin from beta-catenin. Cell 127:139–155PubMedCrossRefGoogle Scholar
  135. Yedavalli VS, Zhang N, Cai H, Zhang P, Starost MF, Hosmane RS, Jeang KT (2008) Ring expanded nucleoside analogues inhibit RNA helicase and intracellular human immunodeficiency virus type 1 replication. J Med Chem 51:5043–5051PubMedPubMedCentralCrossRefGoogle Scholar
  136. Yin J, Park G, Lee JE, Choi EY, Park JY, Kim TH, Park N, Jin X, Jung JE, Shin D, Hong JH, Kim H, Yoo H, Lee SH, Kim YJ, Park JB, Kim JH (2015) DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating miR-21 biogenesis. Brain 138:2553–2570PubMedCrossRefGoogle Scholar
  137. Yoder-Hill J, Pause A, Sonenberg N, Merrick WC (1993) The p46 subunit of eukaryotic initiation factor (eIF)-4F exchanges with eIF-4A. J Biol Chem 268:5566–5573PubMedGoogle Scholar
  138. Yuan B, Wang X, Fan C, You J, Liu Y, Weber JD, Zhong H, Zhang Y (2016) DHX33 transcriptionally controls genes involved in the cell cycle. Mol Cell Biol 36:2903–2917PubMedPubMedCentralCrossRefGoogle Scholar
  139. Zhang Y, Saporita AJ, Weber JD (2013) P19ARF and RasV(1)(2) offer opposing regulation of DHX33 translation to dictate tumor cell fate. Mol Cell Biol 33:1594–1607PubMedPubMedCentralCrossRefGoogle Scholar
  140. Zhang Y, You J, Wang X, Weber J (2015) The DHX33 RNA helicase promotes mRNA translation initiation. Mol Cell Biol 35:2918–2931PubMedPubMedCentralCrossRefGoogle Scholar
  141. Zhong X, Safa AR (2004) RNA helicase A in the MEF1 transcription factor complex up-regulates the MDR1 gene in multidrug-resistant cancer cells. J Biol Chem 279:17134–17141PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of BiochemistryMcGill UniversityMontréalCanada

Personalised recommendations