4cru › Citations

A DDX6-CNOT1 complex and W-binding pockets in CNOT9 reveal direct links between miRNA target recognition and silencing.

Chen Y, Boland A, Kuzuoğlu-Öztürk D, Bawankar P, Loh B, Chang CT, Weichenrieder O, Izaurralde E
Mol Cell 54 737-50 (2014)
Related entries: 4crv, 4crw

Cited: 172 times
EuropePMC logo PMID: 24768540

Abstract

CCR4-NOT is a major effector complex in miRNA-mediated gene silencing. It is recruited to miRNA targets through interactions with tryptophan (W)-containing motifs in TNRC6/GW182 proteins and is required for both translational repression and degradation of miRNA targets. Here, we elucidate the structural basis for the repressive activity of CCR4-NOT and its interaction with TNRC6/GW182s. We show that the conserved CNOT9 subunit attaches to a domain of unknown function (DUF3819) in the CNOT1 scaffold. The resulting complex provides binding sites for TNRC6/GW182, and its crystal structure reveals tandem W-binding pockets located in CNOT9. We further show that the CNOT1 MIF4G domain interacts with the C-terminal RecA domain of DDX6, a translational repressor and decapping activator. The crystal structure of this complex demonstrates striking similarity to the eIF4G-eIF4A complex. Together, our data provide the missing physical links in a molecular pathway that connects miRNA target recognition with translational repression, deadenylation, and decapping.

Reviews - 4cru mentioned but not cited (1)

  1. Regulation of the multisubunit CCR4-NOT deadenylase in the initiation of mRNA degradation. Raisch T, Valkov E. Curr Opin Struct Biol 77 102460 (2022)

Articles - 4cru mentioned but not cited (3)

  1. Ahnak functions as a tumor suppressor via modulation of TGFβ/Smad signaling pathway. Lee IH, Sohn M, Lim HJ, Yoon S, Oh H, Shin S, Shin JH, Oh SH, Kim J, Lee DK, Noh DY, Bae DS, Seong JK, Bae YS. Oncogene 33 4675-4684 (2014)
  2. A CAF40-binding motif facilitates recruitment of the CCR4-NOT complex to mRNAs targeted by Drosophila Roquin. Sgromo A, Raisch T, Bawankar P, Bhandari D, Chen Y, Kuzuoğlu-Öztürk D, Weichenrieder O, Izaurralde E. Nat Commun 8 14307 (2017)
  3. AHNAK controls 53BP1-mediated p53 response by restraining 53BP1 oligomerization and phase separation. Ghodke I, Remisova M, Furst A, Kilic S, Reina-San-Martin B, Poetsch AR, Altmeyer M, Soutoglou E. Mol Cell 81 2596-2610.e7 (2021)


Reviews citing this publication (46)

  1. Towards a molecular understanding of microRNA-mediated gene silencing. Jonas S, Izaurralde E. Nat Rev Genet 16 421-433 (2015)
  2. Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Treiber T, Treiber N, Meister G. Nat Rev Mol Cell Biol 20 5-20 (2019)
  3. The Functions of MicroRNAs: mRNA Decay and Translational Repression. Iwakawa HO, Tomari Y. Trends Cell Biol 25 651-665 (2015)
  4. The complexity of miRNA-mediated repression. Wilczynska A, Bushell M. Cell Death Differ 22 22-33 (2015)
  5. Regulation by 3'-Untranslated Regions. Mayr C. Annu Rev Genet 51 171-194 (2017)
  6. The Ccr4-Not complex is a key regulator of eukaryotic gene expression. Collart MA. Wiley Interdiscip Rev RNA 7 438-454 (2016)
  7. The multiple functions of RNA helicases as drivers and regulators of gene expression. Bourgeois CF, Mortreux F, Auboeuf D. Nat Rev Mol Cell Biol 17 426-438 (2016)
  8. From guide to target: molecular insights into eukaryotic RNA-interference machinery. Ipsaro JJ, Joshua-Tor L. Nat Struct Mol Biol 22 20-28 (2015)
  9. Regulation of global and specific mRNA translation by the mTOR signaling pathway. Nandagopal N, Roux PP. Translation (Austin) 3 e983402 (2015)
  10. Structural Foundations of RNA Silencing by Argonaute. Sheu-Gruttadauria J, MacRae IJ. J Mol Biol 429 2619-2639 (2017)
  11. The conformational plasticity of eukaryotic RNA-dependent ATPases. Ozgur S, Buchwald G, Falk S, Chakrabarti S, Prabu JR, Conti E. FEBS J 282 850-863 (2015)
  12. Multifunctional roles of the mammalian CCR4-NOT complex in physiological phenomena. Shirai YT, Suzuki T, Morita M, Takahashi A, Yamamoto T. Front Genet 5 286 (2014)
  13. Structural and molecular mechanisms for the control of eukaryotic 5'-3' mRNA decay. Mugridge JS, Coller J, Gross JD. Nat Struct Mol Biol 25 1077-1085 (2018)
  14. Deadenylation of mRNA by the CCR4-NOT complex in Drosophila: molecular and developmental aspects. Temme C, Simonelig M, Wahle E. Front Genet 5 143 (2014)
  15. Mechanistic Insights into MicroRNA-Mediated Gene Silencing. Duchaine TF, Fabian MR. Cold Spring Harb Perspect Biol 11 a032771 (2019)
  16. Ciphers and Executioners: How 3'-Untranslated Regions Determine the Fate of Messenger RNAs. Mayya VK, Duchaine TF. Front Genet 10 6 (2019)
  17. MicroRNAs from plants to animals, do they define a new messenger for communication? Li Z, Xu R, Li N. Nutr Metab (Lond) 15 68 (2018)
  18. The organization and regulation of mRNA-protein complexes. Rissland OS. Wiley Interdiscip Rev RNA 8 (2017)
  19. The Interplay between the RNA Decay and Translation Machinery in Eukaryotes. Heck AM, Wilusz J. Cold Spring Harb Perspect Biol 10 a032839 (2018)
  20. Nanos genes and their role in development and beyond. De Keuckelaere E, Hulpiau P, Saeys Y, Berx G, van Roy F. Cell Mol Life Sci 75 1929-1946 (2018)
  21. General and Target-Specific DExD/H RNA Helicases in Eukaryotic Translation Initiation. Shen L, Pelletier J. Int J Mol Sci 21 E4402 (2020)
  22. Modulation of miRNA function by natural and synthetic RNA-binding proteins in cancer. Vos PD, Leedman PJ, Filipovska A, Rackham O. Cell Mol Life Sci 76 3745-3752 (2019)
  23. The multifaceted roles of microRNAs in differentiation. Galagali H, Kim JK. Curr Opin Cell Biol 67 118-140 (2020)
  24. RNA-Binding Proteins in the Regulation of miRNA Activity: A Focus on Neuronal Functions. Loffreda A, Rigamonti A, Barabino SM, Lenzken SC. Biomolecules 5 2363-2387 (2015)
  25. cis-Acting RNA elements in the hepatitis C virus RNA genome. Sagan SM, Chahal J, Sarnow P. Virus Res 206 90-98 (2015)
  26. Anatomy of four human Argonaute proteins. Nakanishi K. Nucleic Acids Res 50 6618-6638 (2022)
  27. A toolbox for miRNA analysis. Svoboda P. FEBS Lett 589 1694-1701 (2015)
  28. The Regulatory Properties of the Ccr4-Not Complex. Chalabi Hagkarim N, Grand RJ. Cells 9 E2379 (2020)
  29. Temporospatial guidance of activity-dependent gene expression by microRNA: mechanisms and functional implications for neural plasticity. Kiltschewskij D, Cairns MJ. Nucleic Acids Res 47 533-545 (2019)
  30. The coupled and uncoupled mechanisms by which trans-acting factors regulate mRNA stability and translation. Fukao A, Fujiwara T. J Biochem 161 309-314 (2017)
  31. The molecular mechanism of translational control via the communication between the microRNA pathway and RNA-binding proteins. Fukao A, Aoyama T, Fujiwara T. RNA Biol 12 922-926 (2015)
  32. Mille viae in eukaryotic mRNA decapping. Valkov E, Jonas S, Weichenrieder O. Curr Opin Struct Biol 47 40-51 (2017)
  33. Ataxin-2: A versatile posttranscriptional regulator and its implication in neural function. Lee J, Kim M, Itoh TQ, Lim C. Wiley Interdiscip Rev RNA 9 e1488 (2018)
  34. Interaction of host cell microRNAs with the HCV RNA genome during infection of liver cells. Sedano CD, Sarnow P. Semin Liver Dis 35 75-80 (2015)
  35. Post-Transcriptional Mechanisms Regulating Epidermal Stem and Progenitor Cell Self-Renewal and Differentiation. Li J, Sen GL. J Invest Dermatol 136 746-752 (2016)
  36. Role of microRNAs in the Development of Cardiovascular Disease in Systemic Autoimmune Disorders. Lopez-Pedrera C, Barbarroja N, Patiño-Trives AM, Luque-Tévar M, Torres-Granados C, Aguirre-Zamorano MA, Collantes-Estevez E, Pérez-Sánchez C. Int J Mol Sci 21 E2012 (2020)
  37. Translation Initiation Regulated by RNA-Binding Protein in Mammals: The Modulation of Translation Initiation Complex by Trans-Acting Factors. Fukao A, Tomohiro T, Fujiwara T. Cells 10 1711 (2021)
  38. Codon optimality in cancer. Gillen SL, Waldron JA, Bushell M. Oncogene 40 6309-6320 (2021)
  39. Mutations in genes encoding regulators of mRNA decapping and translation initiation: links to intellectual disability. Weil D, Piton A, Lessel D, Standart N. Biochem Soc Trans 48 1199-1211 (2020)
  40. Differential expression and emerging functions of non-coding RNAs in cold adaptation. Frigault JJ, Morin MD, Morin PJ. J Comp Physiol B 187 19-28 (2017)
  41. The nexus between RNA-binding proteins and their effectors. He S, Valkov E, Cheloufi S, Murn J. Nat Rev Genet 24 276-294 (2023)
  42. AGO unchained: Canonical and non-canonical roles of Argonaute proteins in mammals. Sala L, Chandrasekhar S, Vidigal JA. Front Biosci (Landmark Ed) 25 1-42 (2020)
  43. Ccr4-Not as a mediator of environmental signaling: a jack of all trades and master of all. Laribee RN. Curr Genet 67 707-713 (2021)
  44. Eukaryotic mRNA decapping factors: molecular mechanisms and activity. He F, Jacobson A. FEBS J 290 5057-5085 (2023)
  45. Regulation of eukaryotic mRNA deadenylation and degradation by the Ccr4-Not complex. Pavanello L, Hall M, Winkler GS. Front Cell Dev Biol 11 1153624 (2023)
  46. Structure and function of molecular machines involved in deadenylation-dependent 5'-3' mRNA degradation. Zhao Q, Pavanello L, Bartlam M, Winkler GS. Front Genet 14 1233842 (2023)

Articles citing this publication (122)

  1. The DEAD-Box Protein Dhh1p Couples mRNA Decay and Translation by Monitoring Codon Optimality. Radhakrishnan A, Chen YH, Martin S, Alhusaini N, Green R, Coller J. Cell 167 122-132.e9 (2016)
  2. Phase Transitions in the Assembly and Function of Human miRISC. Sheu-Gruttadauria J, MacRae IJ. Cell 173 946-957.e16 (2018)
  3. MicroRNAs trigger dissociation of eIF4AI and eIF4AII from target mRNAs in humans. Fukao A, Mishima Y, Takizawa N, Oka S, Imataka H, Pelletier J, Sonenberg N, Thoma C, Fujiwara T. Mol Cell 56 79-89 (2014)
  4. Human DDX6 effects miRNA-mediated gene silencing via direct binding to CNOT1. Rouya C, Siddiqui N, Morita M, Duchaine TF, Fabian MR, Sonenberg N. RNA 20 1398-1409 (2014)
  5. P-body assembly requires DDX6 repression complexes rather than decay or Ataxin2/2L complexes. Ayache J, Bénard M, Ernoult-Lange M, Minshall N, Standart N, Kress M, Weil D. Mol Biol Cell 26 2579-2595 (2015)
  6. MicroRNAs block assembly of eIF4F translation initiation complex in Drosophila. Fukaya T, Iwakawa HO, Tomari Y. Mol Cell 56 67-78 (2014)
  7. GC content shapes mRNA storage and decay in human cells. Courel M, Clément Y, Bossevain C, Foretek D, Vidal Cruchez O, Yi Z, Bénard M, Benassy MN, Kress M, Vindry C, Ernoult-Lange M, Antoniewski C, Morillon A, Brest P, Hubstenberger A, Roest Crollius H, Standart N, Weil D. Elife 8 e49708 (2019)
  8. ATPase activity of the DEAD-box protein Dhh1 controls processing body formation. Mugler CF, Hondele M, Heinrich S, Sachdev R, Vallotton P, Koek AY, Chan LY, Weis K. Elife 5 e18746 (2016)
  9. DDX6 Orchestrates Mammalian Progenitor Function through the mRNA Degradation and Translation Pathways. Wang Y, Arribas-Layton M, Chen Y, Lykke-Andersen J, Sen GL. Mol Cell 60 118-130 (2015)
  10. The DDX6-4E-T interaction mediates translational repression and P-body assembly. Kamenska A, Simpson C, Vindry C, Broomhead H, Bénard M, Ernoult-Lange M, Lee BP, Harries LW, Weil D, Standart N. Nucleic Acids Res 44 6318-6334 (2016)
  11. Cap-binding protein 4EHP effects translation silencing by microRNAs. Chapat C, Jafarnejad SM, Matta-Camacho E, Hesketh GG, Gelbart IA, Attig J, Gkogkas CG, Alain T, Stern-Ginossar N, Fabian MR, Gingras AC, Duchaine TF, Sonenberg N. Proc Natl Acad Sci U S A 114 5425-5430 (2017)
  12. The eIF4E-Binding Protein 4E-T Is a Component of the mRNA Decay Machinery that Bridges the 5' and 3' Termini of Target mRNAs. Nishimura T, Padamsi Z, Fakim H, Milette S, Dunham WH, Gingras AC, Fabian MR. Cell Rep 11 1425-1436 (2015)
  13. miRISC and the CCR4-NOT complex silence mRNA targets independently of 43S ribosomal scanning. Kuzuoğlu-Öztürk D, Bhandari D, Huntzinger E, Fauser M, Helms S, Izaurralde E. EMBO J 35 1186-1203 (2016)
  14. GENE REGULATION. Breakers and blockers—miRNAs at work. Izaurralde E. Science 349 380-382 (2015)
  15. Biochemical isolation of Argonaute protein complexes by Ago-APP. Hauptmann J, Schraivogel D, Bruckmann A, Manickavel S, Jakob L, Eichner N, Pfaff J, Urban M, Sprunck S, Hafner M, Tuschl T, Deutzmann R, Meister G. Proc Natl Acad Sci U S A 112 11841-11845 (2015)
  16. BTG2 bridges PABPC1 RNA-binding domains and CAF1 deadenylase to control cell proliferation. Stupfler B, Birck C, Séraphin B, Mauxion F. Nat Commun 7 10811 (2016)
  17. Reconstitution of Targeted Deadenylation by the Ccr4-Not Complex and the YTH Domain Protein Mmi1. Stowell JAW, Webster MW, Kögel A, Wolf J, Shelley KL, Passmore LA. Cell Rep 17 1978-1989 (2016)
  18. Distinct modes of recruitment of the CCR4-NOT complex by Drosophila and vertebrate Nanos. Raisch T, Bhandari D, Sabath K, Helms S, Valkov E, Weichenrieder O, Izaurralde E. EMBO J 35 974-990 (2016)
  19. Reconstitution of recombinant human CCR4-NOT reveals molecular insights into regulated deadenylation. Raisch T, Chang CT, Levdansky Y, Muthukumar S, Raunser S, Valkov E. Nat Commun 10 3173 (2019)
  20. The LOTUS domain is a conserved DEAD-box RNA helicase regulator essential for the recruitment of Vasa to the germ plasm and nuage. Jeske M, Müller CW, Ephrussi A. Genes Dev 31 939-952 (2017)
  21. The nuclear receptor ERβ engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading. Tarallo R, Giurato G, Bruno G, Ravo M, Rizzo F, Salvati A, Ricciardi L, Marchese G, Cordella A, Rocco T, Gigantino V, Pierri B, Cimmino G, Milanesi L, Ambrosino C, Nyman TA, Nassa G, Weisz A. Genome Biol 18 189 (2017)
  22. Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cells. Freimer JW, Hu TJ, Blelloch R. Elife 7 e38014 (2018)
  23. Importin-β facilitates nuclear import of human GW proteins and balances cytoplasmic gene silencing protein levels. Schraivogel D, Schindler SG, Danner J, Kremmer E, Pfaff J, Hannus S, Depping R, Meister G. Nucleic Acids Res 43 7447-7461 (2015)
  24. Translational repression of the Drosophila nanos mRNA involves the RNA helicase Belle and RNA coating by Me31B and Trailer hitch. Götze M, Dufourt J, Ihling C, Rammelt C, Pierson S, Sambrani N, Temme C, Sinz A, Simonelig M, Wahle E. RNA 23 1552-1568 (2017)
  25. A novel translational control mechanism involving RNA structures within coding sequences. Jungfleisch J, Nedialkova DD, Dotu I, Sloan KE, Martinez-Bosch N, Brüning L, Raineri E, Navarro P, Bohnsack MT, Bohnsack MT, Leidel SA, Díez J. Genome Res 27 95-106 (2017)
  26. ME31B globally represses maternal mRNAs by two distinct mechanisms during the Drosophila maternal-to-zygotic transition. Wang M, Ly M, Lugowski A, Laver JD, Lipshitz HD, Smibert CA, Rissland OS. Elife 6 e27891 (2017)
  27. Role of Ccr4-Not complex in heterochromatin formation at meiotic genes and subtelomeres in fission yeast. Cotobal C, Rodríguez-López M, Duncan C, Hasan A, Yamashita A, Yamamoto M, Bähler J, Mata J. Epigenetics Chromatin 8 28 (2015)
  28. The architecture of the Schizosaccharomyces pombe CCR4-NOT complex. Ukleja M, Cuellar J, Siwaszek A, Kasprzak JM, Czarnocki-Cieciura M, Bujnicki JM, Dziembowski A, Valpuesta JM. Nat Commun 7 10433 (2016)
  29. The RNA helicase DDX6 regulates cell-fate specification in neural stem cells via miRNAs. Nicklas S, Okawa S, Hillje AL, González-Cano L, Del Sol A, Schwamborn JC. Nucleic Acids Res 43 2638-2654 (2015)
  30. A widespread sequence-specific mRNA decay pathway mediated by hnRNPs A1 and A2/B1. Geissler R, Simkin A, Floss D, Patel R, Fogarty EA, Scheller J, Grimson A. Genes Dev 30 1070-1085 (2016)
  31. Argonaute Utilization for miRNA Silencing Is Determined by Phosphorylation-Dependent Recruitment of LIM-Domain-Containing Proteins. Bridge KS, Shah KM, Li Y, Foxler DE, Wong SCK, Miller DC, Davidson KM, Foster JG, Rose R, Hodgkinson MR, Ribeiro PS, Aboobaker AA, Yashiro K, Wang X, Graves PR, Plevin MJ, Lagos D, Sharp TV. Cell Rep 20 173-187 (2017)
  32. General and MicroRNA-Mediated mRNA Degradation Occurs on Ribosome Complexes in Drosophila Cells. Antic S, Wolfinger MT, Skucha A, Hosiner S, Dorner S. Mol Cell Biol 35 2309-2320 (2015)
  33. Not4-dependent translational repression is important for cellular protein homeostasis in yeast. Preissler S, Reuther J, Koch M, Scior A, Bruderek M, Frickey T, Deuerling E. EMBO J 34 1905-1924 (2015)
  34. General decapping activators target different subsets of inefficiently translated mRNAs. He F, Celik A, Wu C, Jacobson A. Elife 7 e34409 (2018)
  35. 4EHP-independent repression of endogenous mRNAs by the RNA-binding protein GIGYF2. Amaya Ramirez CC, Hubbe P, Mandel N, Béthune J. Nucleic Acids Res 46 5792-5808 (2018)
  36. Aubergine and piRNAs promote germline stem cell self-renewal by repressing the proto-oncogene Cbl. Rojas-Ríos P, Chartier A, Pierson S, Simonelig M. EMBO J 36 3194-3211 (2017)
  37. The influence of microRNAs and poly(A) tail length on endogenous mRNA-protein complexes. Rissland OS, Subtelny AO, Wang M, Lugowski A, Nicholson B, Laver JD, Sidhu SS, Smibert CA, Lipshitz HD, Bartel DP. Genome Biol 18 211 (2017)
  38. Codon and amino acid content are associated with mRNA stability in mammalian cells. Forrest ME, Pinkard O, Martin S, Sweet TJ, Hanson G, Coller J. PLoS One 15 e0228730 (2020)
  39. Drosophila Bag-of-marbles directly interacts with the CAF40 subunit of the CCR4-NOT complex to elicit repression of mRNA targets. Sgromo A, Raisch T, Backhaus C, Keskeny C, Alva V, Weichenrieder O, Izaurralde E. RNA 24 381-395 (2018)
  40. Architecture of the ubiquitylation module of the yeast Ccr4-Not complex. Bhaskar V, Basquin J, Conti E. Structure 23 921-928 (2015)
  41. Human GW182 Paralogs Are the Central Organizers for RNA-Mediated Control of Transcription. Hicks JA, Li L, Matsui M, Chu Y, Volkov O, Johnson KC, Corey DR. Cell Rep 20 1543-1552 (2017)
  42. Human Pumilio proteins directly bind the CCR4-NOT deadenylase complex to regulate the transcriptome. Enwerem III, Elrod ND, Chang CT, Lin A, Ji P, Bohn JA, Levdansky Y, Wagner EJ, Valkov E, Goldstrohm AC. RNA 27 445-464 (2021)
  43. A human immune dysregulation syndrome characterized by severe hyperinflammation with a homozygous nonsense Roquin-1 mutation. Tavernier SJ, Athanasopoulos V, Verloo P, Behrens G, Staal J, Bogaert DJ, Naesens L, De Bruyne M, Van Gassen S, Parthoens E, Ellyard J, Cappello J, Morris LX, Van Gorp H, Van Isterdael G, Saeys Y, Lamkanfi M, Schelstraete P, Dehoorne J, Bordon V, Van Coster R, Lambrecht BN, Menten B, Beyaert R, Vinuesa CG, Heissmeyer V, Dullaers M, Haerynck F. Nat Commun 10 4779 (2019)
  44. Cotranslational microRNA mediated messenger RNA destabilization. Tat TT, Maroney PA, Chamnongpol S, Coller J, Nilsen TW. Elife 5 e12880 (2016)
  45. The enzyme activities of Caf1 and Ccr4 are both required for deadenylation by the human Ccr4-Not nuclease module. Maryati M, Airhihen B, Winkler GS. Biochem J 469 169-176 (2015)
  46. Polysome arrest restricts miRNA turnover by preventing exosomal export of miRNA in growth-retarded mammalian cells. Ghosh S, Bose M, Ray A, Bhattacharyya SN. Mol Biol Cell 26 1072-1083 (2015)
  47. A conserved CAF40-binding motif in metazoan NOT4 mediates association with the CCR4-NOT complex. Keskeny C, Raisch T, Sgromo A, Igreja C, Bhandari D, Weichenrieder O, Izaurralde E. Genes Dev 33 236-252 (2019)
  48. NMDAR-dependent Argonaute 2 phosphorylation regulates miRNA activity and dendritic spine plasticity. Rajgor D, Sanderson TM, Amici M, Collingridge GL, Hanley JG. EMBO J 37 e97943 (2018)
  49. The RNA Helicase DDX6 Associates with RIG-I to Augment Induction of Antiviral Signaling. Núñez RD, Budt M, Saenger S, Paki K, Arnold U, Sadewasser A, Wolff T. Int J Mol Sci 19 E1877 (2018)
  50. Essential functions of the CNOT7/8 catalytic subunits of the CCR4-NOT complex in mRNA regulation and cell viability. Mostafa D, Takahashi A, Yanagiya A, Yamaguchi T, Abe T, Kureha T, Kuba K, Kanegae Y, Furuta Y, Yamamoto T, Suzuki T. RNA Biol 17 403-416 (2020)
  51. Xenopus CAF1 requires NOT1-mediated interaction with 4E-T to repress translation in vivo. Waghray S, Williams C, Coon JJ, Wickens M. RNA 21 1335-1345 (2015)
  52. Comprehensive Protein Interactome Analysis of a Key RNA Helicase: Detection of Novel Stress Granule Proteins. Bish R, Cuevas-Polo N, Cheng Z, Hambardzumyan D, Munschauer M, Landthaler M, Vogel C. Biomolecules 5 1441-1466 (2015)
  53. Spatiotemporal Uncoupling of MicroRNA-Mediated Translational Repression and Target RNA Degradation Controls MicroRNP Recycling in Mammalian Cells. Bose M, Barman B, Goswami A, Bhattacharyya SN. Mol Cell Biol 37 e00464-16 (2017)
  54. Casein kinase II promotes target silencing by miRISC through direct phosphorylation of the DEAD-box RNA helicase CGH-1. Alessi AF, Khivansara V, Han T, Freeberg MA, Moresco JJ, Tu PG, Montoye E, Yates JR, Karp X, Kim JK. Proc Natl Acad Sci U S A 112 E7213-22 (2015)
  55. Conservation of miRNA-mediated silencing mechanisms across 600 million years of animal evolution. Mauri M, Kirchner M, Aharoni R, Ciolli Mattioli C, van den Bruck D, Gutkovitch N, Modepalli V, Selbach M, Moran Y, Chekulaeva M. Nucleic Acids Res 45 938-950 (2017)
  56. De Novo Variants in CNOT1, a Central Component of the CCR4-NOT Complex Involved in Gene Expression and RNA and Protein Stability, Cause Neurodevelopmental Delay. Vissers LELM, Kalvakuri S, de Boer E, Geuer S, Oud M, van Outersterp I, Kwint M, Witmond M, Kersten S, Polla DL, Weijers D, Begtrup A, McWalter K, Ruiz A, Gabau E, Morton JEV, Griffith C, Weiss K, Gamble C, Bartley J, Vernon HJ, Brunet K, Ruivenkamp C, Kant SG, Kruszka P, Larson A, Afenjar A, Billette de Villemeur T, Nugent K, DDD Study, Raymond FL, Venselaar H, Demurger F, Soler-Alfonso C, Li D, Bhoj E, Hayes I, Hamilton NP, Ahmad A, Fisher R, van den Born M, Willems M, Sorlin A, Delanne J, Moutton S, Christophe P, Mau-Them FT, Vitobello A, Goel H, Massingham L, Phornphutkul C, Schwab J, Keren B, Charles P, Vreeburg M, De Simone L, Hoganson G, Iascone M, Milani D, Evenepoel L, Revencu N, Ward DI, Burns K, Krantz I, Raible SE, Murrell JR, Wood K, Cho MT, van Bokhoven H, Muenke M, Kleefstra T, Bodmer R, de Brouwer APM. Am J Hum Genet 107 164-172 (2020)
  57. Genome-Wide Mapping of Decay Factor-mRNA Interactions in Yeast Identifies Nutrient-Responsive Transcripts as Targets of the Deadenylase Ccr4. Miller JE, Zhang L, Jiang H, Li Y, Pugh BF, Reese JC. G3 (Bethesda) 8 315-330 (2018)
  58. NB-LRR signaling induces translational repression of viral transcripts and the formation of RNA processing bodies through mechanisms differing from those activated by UV stress and RNAi. Meteignier LV, Zhou J, Cohen M, Bhattacharjee S, Brosseau C, Chan MG, Robatzek S, Moffett P. J Exp Bot 67 2353-2366 (2016)
  59. Whole exome sequencing identifies a recurrent RQCD1 P131L mutation in cutaneous melanoma. Wong SQ, Behren A, Mar VJ, Woods K, Li J, Martin C, Sheppard KE, Wolfe R, Kelly J, Cebon J, Dobrovic A, McArthur GA. Oncotarget 6 1115-1127 (2015)
  60. Inducible and reversible inhibition of miRNA-mediated gene repression in vivo. La Rocca G, King B, Shui B, Li X, Zhang M, Akat KM, Ogrodowski P, Mastroleo C, Chen K, Cavalieri V, Ma Y, Anelli V, Betel D, Vidigal J, Tuschl T, Meister G, Thompson CB, Lindsten T, Haigis K, Ventura A. Elife 10 e70948 (2021)
  61. Modifiers of solid RNP granules control normal RNP dynamics and mRNA activity in early development. Hubstenberger A, Cameron C, Noble SL, Keenan S, Evans TC. J Cell Biol 211 703-716 (2015)
  62. Novel roles of the CCR4-NOT complex. Chapat C, Corbo L. Wiley Interdiscip Rev RNA 5 883-901 (2014)
  63. A continuum of mRNP complexes in embryonic microRNA-mediated silencing. Wu E, Vashisht AA, Chapat C, Flamand MN, Cohen E, Sarov M, Tabach Y, Sonenberg N, Wohlschlegel J, Duchaine TF. Nucleic Acids Res 45 2081-2098 (2017)
  64. Direct role for the Drosophila GIGYF protein in 4EHP-mediated mRNA repression. Ruscica V, Bawankar P, Peter D, Helms S, Igreja C, Izaurralde E. Nucleic Acids Res 47 7035-7048 (2019)
  65. Post-transcriptional gene silencing activity of human GIGYF2. Kryszke MH, Adjeriou B, Liang F, Chen H, Dautry F. Biochem Biophys Res Commun 475 289-294 (2016)
  66. The CCR4-NOT complex maintains liver homeostasis through mRNA deadenylation. Takahashi A, Suzuki T, Soeda S, Takaoka S, Kobori S, Yamaguchi T, Mohamed HMA, Yanagiya A, Abe T, Shigeta M, Furuta Y, Kuba K, Yamamoto T. Life Sci Alliance 3 e201900494 (2020)
  67. Translation is required for miRNA-dependent decay of endogenous transcripts. Biasini A, Abdulkarim B, de Pretis S, Tan JY, Arora R, Wischnewski H, Dreos R, Pelizzola M, Ciaudo C, Marques AC. EMBO J 40 e104569 (2021)
  68. A novel function for the DEAD-box RNA helicase DDX-23 in primary microRNA processing in Caenorhabditis elegans. Chu YD, Chen HK, Huang T, Chan SP. Dev Biol 409 459-472 (2016)
  69. Analysis of mRNA deadenylation by multi-protein complexes. Webster MW, Stowell JAW, Tang TTL, Passmore LA. Methods 126 95-104 (2017)
  70. Crystal structure and functional properties of the human CCR4-CAF1 deadenylase complex. Chen Y, Khazina E, Izaurralde E, Weichenrieder O. Nucleic Acids Res 49 6489-6510 (2021)
  71. DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity. Meijer HA, Schmidt T, Gillen SL, Langlais C, Jukes-Jones R, de Moor CH, Cain K, Wilczynska A, Bushell M. Nucleic Acids Res 47 8224-8238 (2019)
  72. Dual mechanisms regulate the nucleocytoplasmic localization of human DDX6. Huang JH, Ku WC, Chen YC, Chang YL, Chu CY. Sci Rep 7 42853 (2017)
  73. The PIWI protein Aubergine recruits eIF3 to activate translation in the germ plasm. Ramat A, Garcia-Silva MR, Jahan C, Naït-Saïdi R, Dufourt J, Garret C, Chartier A, Cremaschi J, Patel V, Decourcelle M, Bastide A, Juge F, Simonelig M. Cell Res 30 421-435 (2020)
  74. Cellular DEAD-box RNA helicase DDX6 modulates interaction of miR-122 with the 5' untranslated region of hepatitis C virus RNA. Biegel JM, Henderson E, Cox EM, Bonenfant G, Netzband R, Kahn S, Eager R, Pager CT. Virology 507 231-241 (2017)
  75. HELZ directly interacts with CCR4-NOT and causes decay of bound mRNAs. Hanet A, Räsch F, Weber R, Ruscica V, Fauser M, Raisch T, Kuzuoğlu-Öztürk D, Chang CT, Bhandari D, Igreja C, Wohlbold L. Life Sci Alliance 2 e201900405 (2019)
  76. Imaging translational control by Argonaute with single-molecule resolution in live cells. Cialek CA, Galindo G, Morisaki T, Zhao N, Montgomery TA, Stasevich TJ. Nat Commun 13 3345 (2022)
  77. Molecular basis for GIGYF-Me31B complex assembly in 4EHP-mediated translational repression. Peter D, Ruscica V, Bawankar P, Weber R, Helms S, Valkov E, Igreja C, Izaurralde E. Genes Dev 33 1355-1360 (2019)
  78. Early origin and adaptive evolution of the GW182 protein family, the key component of RNA silencing in animals. Zielezinski A, Karlowski WM. RNA Biol 12 761-770 (2015)
  79. The CCR4-NOT deadenylase activity contributes to generation of induced pluripotent stem cells. Zukeran A, Takahashi A, Takaoka S, Mohamed HMA, Suzuki T, Ikematsu S, Yamamoto T. Biochem Biophys Res Commun 474 233-239 (2016)
  80. The DEAD-box RNA-binding protein DDX6 regulates parental RNA decay for cellular reprogramming to pluripotency. Kami D, Kitani T, Nakamura A, Wakui N, Mizutani R, Ohue M, Kametani F, Akimitsu N, Gojo S. PLoS One 13 e0203708 (2018)
  81. Eukaryotic translation initiation factor 4AII contributes to microRNA-122 regulation of hepatitis C virus replication. Ahmed CS, Winlow PL, Parsons AL, Jopling CL. Nucleic Acids Res 46 6330-6343 (2018)
  82. RNF219 attenuates global mRNA decay through inhibition of CCR4-NOT complex-mediated deadenylation. Poetz F, Corbo J, Levdansky Y, Spiegelhalter A, Lindner D, Magg V, Lebedeva S, Schweiggert J, Schott J, Valkov E, Stoecklin G. Nat Commun 12 7175 (2021)
  83. The CCR4-NOT Deadenylase Complex Maintains Adipocyte Identity. Takahashi A, Takaoka S, Kobori S, Yamaguchi T, Ferwati S, Kuba K, Yamamoto T, Suzuki T. Int J Mol Sci 20 E5274 (2019)
  84. The human CNOT1-CNOT10-CNOT11 complex forms a structural platform for protein-protein interactions. Mauxion F, Basquin J, Ozgur S, Rame M, Albrecht J, Schäfer I, Séraphin B, Conti E. Cell Rep 42 111902 (2023)
  85. Alternative splicing of CNOT7 diversifies CCR4-NOT functions. Chapat C, Chettab K, Simonet P, Wang P, De La Grange P, Le Romancer M, Corbo L. Nucleic Acids Res 45 8508-8523 (2017)
  86. CPEB and miR-15/16 Co-Regulate Translation of Cyclin E1 mRNA during Xenopus Oocyte Maturation. Wilczynska A, Git A, Argasinska J, Belloc E, Standart N. PLoS One 11 e0146792 (2016)
  87. Coordinated Regulation of Cap-Dependent Translation and MicroRNA Function by Convergent Signaling Pathways. Olejniczak SH, La Rocca G, Radler MR, Egan SM, Xiang Q, Garippa R, Thompson CB. Mol Cell Biol 36 2360-2373 (2016)
  88. microRNAs stimulate translation initiation mediated by HCV-like IRESes. Mengardi C, Limousin T, Ricci EP, Soto-Rifo R, Decimo D, Ohlmann T. Nucleic Acids Res 45 4810-4824 (2017)
  89. Characterization of the interactions between Codanin-1 and C15Orf41, two proteins implicated in congenital dyserythropoietic anemia type I disease. Swickley G, Bloch Y, Malka L, Meiri A, Noy-Lotan S, Yanai A, Tamary H, Motro B. BMC Mol Cell Biol 21 18 (2020)
  90. DEAD-box helicase 6 (DDX6) is a new negative regulator for milk synthesis and proliferation of bovine mammary epithelial cells. Zhen Z, Zhang M, Yuan X, Qu B, Yu Y, Gao X, Qiu Y. In Vitro Cell Dev Biol Anim 54 52-60 (2018)
  91. Why Is a High Temperature Needed by Thermus thermophilus Argonaute During mRNA Silencing: A Theoretical Study. Liu Y, Yu Z, Zhu J, Wang S, Xu D, Han W. Front Chem 6 223 (2018)
  92. Building on the Ccr4-Not architecture. Villanyi Z, Collart MA. Bioessays 38 997-1002 (2016)
  93. Dedicated chaperones coordinate co-translational regulation of ribosomal protein production with ribosome assembly to preserve proteostasis. Pillet B, Méndez-Godoy A, Murat G, Favre S, Stumpe M, Falquet L, Kressler D. Elife 11 e74255 (2022)
  94. RNA binding proteins Smaug and Cup induce CCR4-NOT-dependent deadenylation of the nanos mRNA in a reconstituted system. Pekovic F, Rammelt C, Kubíková J, Metz J, Jeske M, Wahle E. Nucleic Acids Res 51 3950-3970 (2023)
  95. Roles of mRNA fate modulators Dhh1 and Pat1 in TNRC6-dependent gene silencing recapitulated in yeast. Makino S, Mishima Y, Inoue K, Inada T. J Biol Chem 290 8331-8347 (2015)
  96. The Route of Infection Influences the Contribution of Key Immunity Genes to Antibacterial Defense in Anopheles gambiae. Dekmak AS, Yang X, Zu Dohna H, Buchon N, Osta MA. J Innate Immun 13 107-126 (2021)
  97. Trinucleotide repeat containing 6c (TNRC6c) is essential for microvascular maturation during distal airspace sacculation in the developing lung. Guo H, Kazadaeva Y, Ortega FE, Manjunath N, Desai TJ. Dev Biol 430 214-223 (2017)
  98. Uncovering a novel function of the CCR4-NOT complex in phytochrome A-mediated light signalling in plants. Schwenk P, Sheerin DJ, Ponnu J, Staudt AM, Lesch KL, Lichtenberg E, Medzihradszky KF, Hoecker U, Klement E, Viczián A, Hiltbrunner A. Elife 10 e63697 (2021)
  99. Involvement of DDX6 gene in radio- and chemoresistance in glioblastoma. Cho YJ, Kang W, Kim SH, Sa JK, Kim N, Paddison PJ, Kim M, Joo KM, Hwang YI, Nam DH. Int J Oncol 48 1053-1062 (2016)
  100. Structural characterisation of TNRC6A nuclear localisation signal in complex with importin-alpha. Chaston JJ, Stewart AG, Christie M. PLoS One 12 e0183587 (2017)
  101. The RNA helicase DDX6 controls early mouse embryogenesis by repressing aberrant inhibition of BMP signaling through miRNA-mediated gene silencing. Kim J, Muraoka M, Okada H, Toyoda A, Ajima R, Saga Y. PLoS Genet 18 e1009967 (2022)
  102. eIF4A2 targets developmental potency and histone H3.3 transcripts for translational control of stem cell pluripotency. Li D, Yang J, Huang X, Zhou H, Wang J. Sci Adv 8 eabm0478 (2022)
  103. Mutations in the NOT Genes or in the Translation Machinery Similarly Display Increased Resistance to Histidine Starvation. Collart MA, Kassem S, Villanyi Z. Front Genet 8 61 (2017)
  104. Phytochrome A Mediates the Disassembly of Processing Bodies in Far-Red Light. Schwenk P, Hiltbrunner A. Front Plant Sci 13 828529 (2022)
  105. RNA-binding proteins in mouse male germline stem cells: a mammalian perspective. Qi H. Cell Regen 5 1 (2016)
  106. Rapid Gene Evolution in an Ancient Post-transcriptional and Translational Regulatory System Compensates for Meiotic X Chromosomal Inactivation. Xia S, Ventura IM, Blaha A, Sgromo A, Han S, Izaurralde E, Long M. Mol Biol Evol 39 msab296 (2022)
  107. 1-Hydroxy-xanthine derivatives inhibit the human Caf1 nuclease and Caf1-containing nuclease complexes via Mg2+-dependent binding. Airhihen B, Pavanello L, Jadhav GP, Fischer PM, Winkler GS. FEBS Open Bio 9 717-727 (2019)
  108. A functional screen of RNA binding proteins identifies genes that promote or limit the accumulation of CD138+ plasma cells. Turner DJ, Saveliev A, Salerno F, Matheson LS, Screen M, Lawson H, Wotherspoon D, Kranc KR, Turner M. Elife 11 e72313 (2022)
  109. Physiologically relevant miRNAs in mammalian oocytes are rare and highly abundant. Kataruka S, Kinterova V, Horvat F, Kulmann MIR, Kanka J, Svoboda P. EMBO Rep 23 e53514 (2022)
  110. The functional characterization of phosphorylation of tristetraprolin at C-terminal NOT1-binding domain. Hsieh HH, Chen YA, Chang YJ, Wang HH, Yu YH, Lin SW, Huang YJ, Lin S, Chang CJ. J Inflamm (Lond) 18 22 (2021)
  111. Cooperative regulation of coupled oncoprotein synthesis and stability in triple-negative breast cancer by EGFR and CDK12/13. Ang HX, Sutiman N, Deng XL, Liu A, Cerda-Smith CG, Hutchinson HM, Kim H, Bartelt LC, Chen Q, Barrera A, Lin J, Sheng Z, McDowell IC, Reddy TE, Nicchitta CV, Wood KC. Proc Natl Acad Sci U S A 120 e2221448120 (2023)
  112. Identification of Phosphorylated Amino Acids in Human TNRC6A C-Terminal Region and Their Effects on the Interaction with the CCR4-NOT Complex. Munakata F, Suzawa M, Ui-Tei K. Genes (Basel) 12 271 (2021)
  113. Integrative data analysis indicates an intrinsic disordered domain character of Argonaute-binding motifs. Zielezinski A, Karlowski WM. Bioinformatics 31 332-339 (2015)
  114. Synonymous codon usage regulates translation initiation. Barrington CL, Galindo G, Koch AL, Horton ER, Morrison EJ, Tisa S, Stasevich TJ, Rissland OS. Cell Rep 42 113413 (2023)
  115. Translation control: Learning from viruses, again. Díez J, Jungfleisch J. RNA Biol 14 835-837 (2017)
  116. MiRNA 3613-5p and MiRNA 3916 rescued the inhibition of cell migration in CNOT2 depleted MDA-MD-231 cells. Sohn EJ. Transl Cancer Res 9 4542-4549 (2020)
  117. RNF219 regulates CCR4-NOT function in mRNA translation and deadenylation. Guénolé A, Velilla F, Chartier A, Rich A, Carvunis AR, Sardet C, Simonelig M, Sobhian B. Sci Rep 12 9288 (2022)
  118. Reconstitution of Human CCR4-NOT Complex from Purified Proteins and an Assay of Its Deadenylation Activity. Levdansky Y, Valkov E. Methods Mol Biol 2723 1-17 (2024)
  119. Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2. Suzuki T, Hoshina M, Nishijima S, Hoshina N, Kikuguchi C, Tomohiro T, Fukao A, Fujiwara T, Yamamoto T. RNA Biol 19 234-246 (2022)
  120. SUZ domain-containing proteins have multiple effects on nonsense-mediated decay target transcripts. Halbout M, Bury M, Hanet A, Gerin I, Graff J, Killian T, Gatto L, Vertommen D, Bommer GT. J Biol Chem 299 105095 (2023)
  121. The Dynamic Poly(A) Tail Acts as a Signal Hub in mRNA Metabolism. Zhang G, Luo H, Li X, Hu Z, Wang Q. Cells 12 572 (2023)
  122. miR-148a-3p and DDX6 functional link promotes survival of myeloid leukemia cells. Ghashghaei M, Le CT, Shaalan H, Escano L, Yue M, Arsalan A, Rouhi A, Nguyen TA, Vu LP. Blood Adv 7 3846-3861 (2023)


Quick links