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Mechanism and regulation of the nonsense-mediated decay pathway

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Hug, Nele, Longman, Dasa, Cáceres, Javier F.·2016·Nucleic Acids Research
DOI 10.1093/nar/gkw010PMC PMC4770240
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Abstract

The Nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs) but also regulates the abundance of a large number of cellular RNAs. The central role of NMD in the control of gene expression requires the existence of buffering mechanisms that tightly regulate the magnitude of this pathway. Here, we will focus on the mechanism of NMD with an emphasis on the role of RNA helicases in the transition from NMD complexes that recognize a PTC to those that promote mRNA decay. We will also review recent strategies aimed at uncovering novel trans-acting factors and their functional role in the NMD pathway. Finally, we will describe recent progress in the study of the physiological role of the NMD response.

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  • The chance of nonsense mediated decay upon stop-codon induction is highest if the codon is at least 50 base pairs upstream of an exon-exon junction.

    “The chance of nonsense mediated decay upon stop-codon induction is the highest if the codon is at least 50 base pairs upstream of an exon-exon junction.42”

    From Protocol to create isogenic disease models from adult stem cell-derived organoids using next-generation CRISPR tools (2024) · cites this paper as [42]

    The Introduction’s “PTC definition” section says that, in mammals, mRNAs with a premature termination codon 50–55 nucleotides upstream of the final exon–exon junction are efficiently degraded. That supports the positional link, but the citing sentence omits the mammalian and final-junction qualifiers and says the chance is “highest,” a comparison the passage does not make. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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  1. [1]Isken O. Maquat L.E. Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function Genes Dev. 2007 21 1833 1856 17671086
  2. [3]Schweingruber C. Rufener S.C. Zünd D. Yamashita A. Mühlemann O. Nonsense-mediated mRNA decay - mechanisms of substrate mRNA recognition and degradation in mammalian cells Biochim. Biophys. Acta 2013 1829 612 623 23435113
  3. [4]Bhuvanagiri M. Schlitter A.M. Hentze M.W. Kulozik A.E. NMD: RNA biology meets human genetic medicine Biochem. J. 2010 430 365 377 20795950
  4. [5]Miller J.N. Pearce D.A. Nonsense-mediated decay in genetic disease: friend or foe Mutat. Res. Rev. Mutat. Res. 2014 762 52 64 25485595 PMC4260155
  5. [6]Alonso C.R. Nonsense-mediated RNA decay: a molecular system micromanaging individual gene activities and suppressing genomic noise Bioessays 2005 27 463 466 15832387
  6. [7]Chang Y.-F. Imam J.S. Wilkinson M.F. The nonsense-mediated decay RNA surveillance pathway Annu. Rev. Biochem. 2007 76 51 74 17352659
  7. [8]Palacios I.M. Nonsense-mediated mRNA decay: from mechanistic insights to impacts on human health Brief. Funct. Genomics 2013 12 25 36 23148322
  8. [9]Huang L. Lou C.-H. Chan W. Shum E.Y. Shao A. Stone E. Karam R. Song H.-W. Wilkinson M.F. RNA homeostasis governed by cell type-specific and branched feedback loops acting on NMD Mol. Cell 2011 43 950 961 21925383 PMC4281029
  9. [10]Yepiskoposyan H. Aeschimann F. Nilsson D. Okoniewski M. Mühlemann O. Autoregulation of the nonsense-mediated mRNA decay pathway in human cells RNA 2011 17 2108 2118 22028362 PMC3222124
  10. [11]Longman D. Hug N. Keith M. Anastasaki C. Patton E.E. Grimes G. Cáceres J.F. DHX34 and NBAS form part of an autoregulatory NMD circuit that regulates endogenous RNA targets in human cells, zebrafish and Caenorhabditis elegans Nucleic Acids Res. 2013 41 8319 8331 23828042 PMC3783168
  11. [12]Degtiar E. Fridman A. Gottlieb D. Vexler K. Berezin I. Farhi R. Golani L. Shaul O. The feedback control of UPF3 is crucial for RNA surveillance in plants Nucleic Acids Res. 2015 43 4219 4235 25820429 PMC4417159
  12. [13]Nguyen L.S. Wilkinson M.F. Gecz J. Nonsense-mediated mRNA decay: inter-individual variability and human disease Neurosci. Biobehav. Rev. 2014 46 Pt 2 175 186 24239855 PMC4021004
  13. [14]Hurt J.A. Robertson A.D. Burge C.B. Global analyses of UPF1 binding and function reveal expanded scope of nonsense-mediated mRNA decay Genome Res. 2013 23 1636 1650 23766421 PMC3787261
  14. [15]Kurihara Y. Matsui A. Hanada K. Kawashima M. Ishida J. Morosawa T. Tanaka M. Kaminuma E. Mochizuki Y. Matsushima A. Genome-wide suppression of aberrant mRNA-like noncoding RNAs by NMD in Arabidopsis Proc. Natl. Acad. Sci. U.S.A. 2009 106 2453 2458 19181858 PMC2650177
  15. [16]Smith J.E. Alvarez-Dominguez J.R. Kline N. Huynh N.J. Geisler S. Hu W. Coller J. Baker K.E. Translation of small open reading frames within unannotated RNA transcripts in Saccharomyces cerevisiae Cell Rep. 2014 7 1858 1866 24931603 PMC4105149
  16. [17]Smith J.E. Baker K.E. Nonsense-mediated RNA decay–a switch and dial for regulating gene expression Bioessays 2015 37 612 623 25820233 PMC4454373
  17. [18]Nagy E. Maquat L.E. A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance Trends Biochem. Sci. 1998 23 198 199 9644970
  18. [20]Zhang J. Sun X. Qian Y. LaDuca J.P. Maquat L.E. At least one intron is required for the nonsense-mediated decay of triosephosphate isomerase mRNA: a possible link between nuclear splicing and cytoplasmic translation Mol. Cell. Biol. 1998 18 5272 5283 9710612 PMC109113
  19. [21]Zhang J. Sun X. Qian Y. Maquat L.E. Intron function in the nonsense-mediated decay of beta-globin mRNA: indications that pre-mRNA splicing in the nucleus can influence mRNA translation in the cytoplasm RNA 1998 4 801 815 9671053 PMC1369660
  20. [22]Le Hir H. Gatfield D. Izaurralde E. Moore M.J. The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay EMBO J. 2001 20 4987 4997 11532962 PMC125616
  21. [23]Lykke-Andersen J. Shu M.D. Steitz J.A. Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1 Science 2001 293 1836 1839 11546874
  22. [24]Gehring N.H. Lamprinaki S. Kulozik A.E. Hentze M.W. Disassembly of exon junction complexes by PYM Cell 2009 137 536 548 19410547
  23. [25]Le Hir H. Séraphin B. EJCs at the heart of translational control Cell 2008 133 213 216 18423193
  24. [26]Bono F. Gehring N.H. Assembly, disassembly and recycling: the dynamics of exon junction complexes RNA Biol. 2011 8 24 29 21289489 PMC3127076
  25. [27]Singh G. Kucukural A. Cenik C. Leszyk J.D. Shaffer S.A. Weng Z. Moore M.J. The cellular EJC interactome reveals higher-order mRNP structure and an EJC-SR protein nexus Cell 2012 151 750 764 23084401 PMC3522173
  26. [28]Saulière J. Murigneux V. Wang Z. Marquenet E. Barbosa I. Le Tonquèze O. Audic Y. Paillard L. Roest Crollius H. Le Hir H. CLIP-seq of eIF4AIII reveals transcriptome-wide mapping of the human exon junction complex Nat. Struct. Mol. Biol. 2012 19 1124 1131 23085716
  27. [29]Le Hir H. Saulière J. Wang Z. The exon junction complex as a node of post-transcriptional networks Nat. Rev. Mol. Cell Biol. 2016 17 41 54 26670016
  28. [30]Amrani N. Ganesan R. Kervestin S. Mangus D.A. Ghosh S. Jacobson A. A faux 3′-UTR promotes aberrant termination and triggers nonsense-mediated mRNA decay Nature 2004 432 112 118 15525991
  29. [31]Amrani N. Sachs M.S. Jacobson A. Early nonsense: mRNA decay solves a translational problem Nat. Rev. Mol. Cell Biol. 2006 7 415 425 16723977
  30. [32]Wen J. Brogna S. Splicing-dependent NMD does not require the EJC in Schizosaccharomyces pombe EMBO J. 2010 29 1537 1551 20360683 PMC2876954
  31. [33]Gatfield D. Unterholzner L. Ciccarelli F.D. Bork P. Izaurralde E. Nonsense-mediated mRNA decay in Drosophila: at the intersection of the yeast and mammalian pathways EMBO J. 2003 22 3960 3970 12881430 PMC169044
  32. [34]Longman D. Plasterk R.H.A. Johnstone I.L. Cáceres J.F. Mechanistic insights and identification of two novel factors in the C. elegans NMD pathway Genes Dev. 2007 21 1075 1085 17437990 PMC1855233
  33. [35]Hodgkin J. Papp A. Pulak R. Ambros V. Anderson P. A new kind of informational suppression in the nematode Caenorhabditis elegans Genetics 1989 123 301 313 2583479 PMC1203802
  34. [36]Pulak R. Anderson P. mRNA surveillance by the Caenorhabditis elegans smg genes Genes Dev. 1993 7 1885 1897 8104846
  35. [37]Leeds P. Peltz S.W. Jacobson A. Culbertson M.R. The product of the yeast UPF1 gene is required for rapid turnover of mRNAs containing a premature translational termination codon Genes Dev. 1991 5 2303 2314 1748286
  36. [38]Leeds P. Wood J.M. Lee B.S. Culbertson M.R. Gene products that promote mRNA turnover in Saccharomyces cerevisiae Mol. Cell. Biol. 1992 12 2165 2177 1569946 PMC364388
  37. [39]Mühlemann O. Eberle A.B. Stalder L. Zamudio Orozco R. Recognition and elimination of nonsense mRNA Biochim. Biophys. Acta 2008 1779 538 549 18657639
  38. [40]Cordin O. Banroques J. Tanner N.K. Linder P. The DEAD-box protein family of RNA helicases Gene 2006 367 17 37 16337753
  39. [41]Rajkowitsch L. Chen D. Stampfl S. Semrad K. Waldsich C. Mayer O. Jantsch M.F. Konrat R. Bläsi U. Schroeder R. RNA chaperones, RNA annealers and RNA helicases RNA Biol. 2007 4 118 130 18347437
  40. [42]Denning G. Jamieson L. Maquat L.E. Thompson E.A. Fields A.P. Cloning of a novel phosphatidylinositol kinase-related kinase: characterization of the human SMG-1 RNA surveillance protein J. Biol. Chem. 2001 276 22709 22714 11331269
  41. [43]Grimson A. O'Connor S. Newman C.L. Anderson P. SMG-1 is a phosphatidylinositol kinase-related protein kinase required for nonsense-mediated mRNA Decay in Caenorhabditis elegans Mol. Cell. Biol. 2004 24 7483 7490 15314158 PMC506987
  42. [44]Yamashita A. Ohnishi T. Kashima I. Taya Y. Ohno S. Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay Genes Dev. 2001 15 2215 2228 11544179 PMC312771
  43. [45]Yamashita A. Izumi N. Kashima I. Ohnishi T. Saari B. Katsuhata Y. Muramatsu R. Morita T. Iwamatsu A. Hachiya T. SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate remodeling of the mRNA surveillance complex during nonsense-mediated mRNA decay Genes Dev. 2009 23 1091 1105 19417104 PMC2682953
  44. [46]Fernández I.S. Yamashita A. Arias-Palomo E. Bamba Y. Bartolomé R.A. Canales M.A. Teixidó J. Ohno S. Llorca O. Characterization of SMG-9, an essential component of the nonsense-mediated mRNA decay SMG1C complex Nucleic Acids Res. 2011 39 347 358 20817927 PMC3017601
  45. [47]Arias-Palomo E. Yamashita A. Fernández I.S. Núñez-Ramírez R. Bamba Y. Izumi N. Ohno S. Llorca O. The nonsense-mediated mRNA decay SMG-1 kinase is regulated by large-scale conformational changes controlled by SMG-8 Genes Dev. 2011 25 153 164 21245168 PMC3022261
  46. [48]Kashima I. Yamashita A. Izumi N. Kataoka N. Morishita R. Hoshino S. Ohno M. Dreyfuss G. Ohno S. Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay Genes Dev. 2006 20 355 367 16452507 PMC1361706
  47. [49]Melero R. Uchiyama A. Castaño R. Kataoka N. Kurosawa H. Ohno S. Yamashita A. Llorca O. Structures of SMG1-UPFs complexes: SMG1 contributes to regulate UPF2-dependent activation of UPF1 in NMD Structure 2014 22 1105 1119 25002321
  48. [50]Deniaud A. Karuppasamy M. Bock T. Masiulis S. Huard K. Garzoni F. Kerschgens K. Hentze M.W. Kulozik A.E. Beck M. A network of SMG-8, SMG-9 and SMG-1 C-terminal insertion domain regulates UPF1 substrate recruitment and phosphorylation Nucleic Acids Res. 2015 43 7600 7611 26130714 PMC4551919
  49. [51]Chakrabarti S. Jayachandran U. Bonneau F. Fiorini F. Basquin C. Domcke S. Le Hir H. Conti E. Molecular mechanisms for the RNA-dependent ATPase activity of Upf1 and its regulation by Upf2 Mol. Cell 2011 41 693 703 21419344
  50. [52]Chamieh H. Ballut L. Bonneau F. Le Hir H. NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity Nat. Struct. Mol. Biol. 2008 15 85 93 18066079
  51. [53]Fiorini F. Boudvillain M. Le Hir H. Tight intramolecular regulation of the human Upf1 helicase by its N- and C-terminal domains Nucleic Acids Res. 2013 41 2404 2415 23275559 PMC3575847
  52. [54]Clerici M. Mourão A. Gutsche I. Gehring N.H. Hentze M.W. Kulozik A. Kadlec J. Sattler M. Cusack S. Unusual bipartite mode of interaction between the nonsense-mediated decay factors, UPF1 and UPF2 EMBO J. 2009 28 2293 22306 19556969 PMC2726699
  53. [55]Franks T.M. Singh G. Lykke-Andersen J. Upf1 ATPase-dependent mRNP disassembly is required for completion of nonsense- mediated mRNA decay Cell 2010 143 938 950 21145460 PMC3357093
  54. [56]Fiorini F. Bagchi D. Le Hir H. Croquette V. Human Upf1 is a highly processive RNA helicase and translocase with RNP remodelling activities Nat. Commun. 2015 6 7581 26138914 PMC4506499
  55. [57]Melero R. Buchwald G. Castaño R. Raabe M. Gil D. Lázaro M. Urlaub H. Conti E. Llorca O. The cryo-EM structure of the UPF-EJC complex shows UPF1 poised toward the RNA 3′ end Nat. Struct. Mol. Biol. 2012 19 498 505 22522823
  56. [58]Schoenberg D.R. Maquat L.E. Regulation of cytoplasmic mRNA decay Nat. Rev. Genet. 2012 13 246 259 22392217 PMC3351101
  57. [59]Eberle A.B. Lykke-Andersen S. Mühlemann O. Jensen T.H. SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells Nat. Struct. Mol. Biol. 2009 16 49 55 19060897
  58. [60]Okada-Katsuhata Y. Yamashita A. Kutsuzawa K. Izumi N. Hirahara F. Ohno S. N- and C-terminal Upf1 phosphorylations create binding platforms for SMG-6 and SMG-5:SMG-7 during NMD Nucleic Acids Res. 2012 40 1251 1266 21965535 PMC3273798
  59. [61]Chakrabarti S. Bonneau F. Schüssler S. Eppinger E. Conti E. Phospho-dependent and phospho-independent interactions of the helicase UPF1 with the NMD factors SMG5-SMG7 and SMG6 Nucleic Acids Res. 2014 42 9447 9460 25013172 PMC4132714
  60. [62]Nicholson P. Josi C. Kurosawa H. Yamashita A. Mühlemann O. A novel phosphorylation-independent interaction between SMG6 and UPF1 is essential for human NMD Nucleic Acids Res. 2014 42 9217 9235 25053839 PMC4132754
  61. [63]Huntzinger E. Kashima I. Fauser M. Saulière J. Izaurralde E. SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan RNA 2008 14 2609 2617 18974281 PMC2590965
  62. [64]Schmidt S.A. Foley P.L. Jeong D.-H. Rymarquis L.A. Doyle F. Tenenbaum S.A. Belasco J.G. Green P.J. Identification of SMG6 cleavage sites and a preferred RNA cleavage motif by global analysis of endogenous NMD targets in human cells Nucleic Acids Res. 2014 43 309 323 25429978 PMC4288159
  63. [65]Lykke-Andersen S. Chen Y. Ardal B.R. Lilje B. Waage J. Sandelin A. Jensen T.H. Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes Genes Dev. 2014 28 2498 2517 25403180 PMC4233243
  64. [66]Lykke-Andersen J. Bennett E.J. Protecting the proteome: eukaryotic cotranslational quality control pathways J. Cell Biol. 2014 204 467 476 24535822 PMC3926952
  65. [67]Loh B. Jonas S. Izaurralde E. The SMG5-SMG7 heterodimer directly recruits the CCR4-NOT deadenylase complex to mRNAs containing nonsense codons via interaction with POP2 Genes Dev. 2013 27 2125 2138 24115769 PMC3850096
  66. [68]Unterholzner L. Izaurralde E. SMG7 acts as a molecular link between mRNA surveillance and mRNA decay Mol. Cell 2004 16 587 596 15546618
  67. [69]Gehring N.H. Kunz J.B. Neu-Yilik G. Breit S. Viegas M.H. Hentze M.W. Kulozik A.E. Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements Mol. Cell 2005 20 65 75 16209946
  68. [70]Chan W.-K. Huang L. Gudikote J.P. Chang Y.-F. Imam J.S. MacLean J.A. Wilkinson M.F. An alternative branch of the nonsense-mediated decay pathway EMBO J. 2007 26 1820 1830 17363904 PMC1847659
  69. [71]Ivanov P. V Gehring N.H. Kunz J.B. Hentze M.W. Kulozik A.E. Interactions between UPF1, eRFs, PABP and the exon junction complex suggest an integrated model for mammalian NMD pathways EMBO J. 2008 27 736 747 18256688 PMC2265754
  70. [72]Andersen C.B.F. Ballut L. Johansen J.S. Chamieh H. Nielsen K.H. Oliveira C.L.P. Pedersen J.S. Séraphin B. Le Hir H. Andersen G.R. Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA Science 2006 313 1968 1972 16931718
  71. [73]Bono F. Ebert J. Lorentzen E. Conti E. The crystal structure of the exon junction complex reveals how it maintains a stable grip on mRNA Cell 2006 126 713 725 16923391
  72. [74]Ballut L. Marchadier B. Baguet A. Tomasetto C. Séraphin B. Le Hir H. The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity Nat. Struct. Mol. Biol. 2005 12 861 869 16170325
  73. [75]Noble C.G. Song H. MLN51 stimulates the RNA-helicase activity of eIF4AIII PLoS One 2007 2 e303 17375189 PMC1810427
  74. [76]Le Hir H. Moore M.J. Maquat L.E. Pre-mRNA splicing alters mRNP composition: evidence for stable association of proteins at exon-exon junctions Genes Dev. 2000 14 1098 1108 10809668 PMC316578
  75. [77]Gehring N.H. Neu-Yilik G. Schell T. Hentze M.W. Kulozik A.E. Y14 and hUpf3b form an NMD-activating complex Mol. Cell 2003 11 939 949 12718880
  76. [78]Geißler V. Altmeyer S. Stein B. Uhlmann-Schiffler H. Stahl H. The RNA helicase Ddx5/p68 binds to hUpf3 and enhances NMD of Ddx17/p72 and Smg5 mRNA Nucleic Acids Res. 2013 41 7875 7888 23788676 PMC3763533
  77. [79]Izumi N. Yamashita A. Iwamatsu A. Kurata R. Nakamura H. Saari B. Hirano H. Anderson P. Ohno S. AAA+ proteins RUVBL1 and RUVBL2 coordinate PIKK activity and function in nonsense-mediated mRNA decay Sci. Signaling 2010 3 ra27 20371770
  78. [80]Hug N. Cáceres J.F. The RNA helicase DHX34 activates NMD by promoting a transition from the surveillance to the decay-inducing complex Cell Rep. 2014 8 1845 1856 25220460 PMC4534575
  79. [81]Schwer B. A new twist on RNA helicases: DExH/D box proteins as RNPases Nat. Struct. Biol. 2001 8 113 116 11175897
  80. [82]Jankowsky E. Bowers H. Remodeling of ribonucleoprotein complexes with DExH/D RNA helicases Nucleic Acids Res. 2006 34 4181 4188 16935886 PMC1616955
  81. [83]Hogg J.R. Goff S.P. Upf1 senses 3′ UTR length to potentiate mRNA decay Cell 2010 143 379 389 21029861 PMC2981159
  82. [84]Kurosaki T. Maquat L.E. Rules that govern UPF1 binding to mRNA 3′ UTRs Proc. Natl. Acad. Sci. U.S.A. 2013 110 3357 3362 23404710 PMC3587222
  83. [85]Sievers C. Schlumpf T. Sawarkar R. Comoglio F. Paro R. Mixture models and wavelet transforms reveal high confidence RNA-protein interaction sites in MOV10 PAR-CLIP data Nucleic Acids Res. 2012 40 e160 22844102 PMC3488208
  84. [86]Gregersen L.H. Schueler M. Munschauer M. Mastrobuoni G. Chen W. Kempa S. Dieterich C. Landthaler M. MOV10 is a 5′ to 3′ RNA helicase contributing to UPF1 mRNA target degradation by translocation along 3′ UTRs Mol. Cell 2014 54 573 585 24726324
  85. [87]Bühler M. Steiner S. Mohn F. Paillusson A. Mühlemann O. EJC-independent degradation of nonsense immunoglobulin-mu mRNA depends on 3′ UTR length Nat. Struct. Mol. Biol. 2006 13 462 464 16622410
  86. [88]He F. Jacobson A. Nonsense-mediated mRNA decay: degradation of defective transcripts is only part of the story Annu. Rev. Genet. 2015 49 339 366 26436458 PMC4837945
  87. [89]Zünd D. Gruber A.R. Zavolan M. Mühlemann O. Translation-dependent displacement of UPF1 from coding sequences causes its enrichment in 3′ UTRs Nat. Struct. Mol. Biol. 2013 20 936 943 23832275
  88. [90]Tani H. Imamachi N. Salam K.A. Mizutani R. Ijiri K. Irie T. Yada T. Suzuki Y. Akimitsu N. Identification of hundreds of novel UPF1 target transcripts by direct determination of whole transcriptome stability RNA Biol. 2014 6 1370 1379 PMC3597577 23064114
  89. [91]Kurosaki T. Li W. Hoque M. Popp M.W.-L. Ermolenko D.N. Tian B. Maquat L.E. A post-translational regulatory switch on UPF1 controls targeted mRNA degradation Genes Dev. 2014 28 1900 1916 25184677 PMC4197951
  90. [92]Lee S.R. Pratt G.A. Martinez F.J. Yeo G.W. Lykke-Andersen J. Target discrimination in nonsense-mediated mRNA decay requires Upf1 ATPase activity Mol. Cell 2015 59 413 425 26253027 PMC4673969
  91. [93]Fatscher T. Boehm V. Gehring N.H. Mechanism, factors, and physiological role of nonsense-mediated mRNA decay Cell. Mol. Life Sci. 2015 72 4523 4544 26283621 PMC11113733
  92. [94]Eberle A.B. Stalder L. Mathys H. Orozco R.Z. Mühlemann O. Posttranscriptional gene regulation by spatial rearrangement of the 3′ untranslated region PLoS Biol. 2008 6 e92 18447580 PMC2689704
  93. [95]Singh G. Rebbapragada I. Lykke-Andersen J. A competition between stimulators and antagonists of Upf complex recruitment governs human nonsense-mediated mRNA decay PLoS Biol. 2008 6 e111 18447585 PMC2689706
  94. [96]Mendell J.T. Sharifi N.A. Meyers J.L. Martinez-Murillo F. Dietz H.C. Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise Nat. Genet. 2004 36 1073 1078 15448691
  95. [97]Wittmann J. Hol E.M. Jäck H.-M. hUPF2 silencing identifies physiologic substrates of mammalian nonsense-mediated mRNA decay Mol. Cell. Biol. 2006 26 1272 1287 16449641 PMC1367210
  96. [98]Weischenfeldt J. Damgaard I. Bryder D. Theilgaard-Mönch K. Thoren L. a Nielsen F.C. Jacobsen S.E.W. Nerlov C. Porse B.T. NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements Genes Dev. 2008 22 1381 1396 18483223 PMC2377192
  97. [99]Nicholson P. Yepiskoposyan H. Metze S. Zamudio Orozco R. Kleinschmidt N. Mühlemann O. Nonsense-mediated mRNA decay in human cells: mechanistic insights, functions beyond quality control and the double-life of NMD factors Cell. Mol. Life Sci. 2010 67 677 700 19859661 PMC11115722
  98. [100]Zarkower D. De Bono M. Aronoff R. Hodgkin J. Regulatory rearrangements and smg-sensitive alleles of the C. elegans sex-determining gene tra-1 Dev. Genet. 1994 15 240 250 7520378
  99. [101]Cho H. Kim K.M. Kim Y.K. Human proline-rich nuclear receptor coregulatory protein 2 mediates an interaction between mRNA surveillance machinery and decapping complex Mol. Cell 2009 33 75 86 19150429
  100. [102]Lai T. Cho H. Liu Z. Bowler M.W. Piao S. Parker R. Kim Y.K. Song H. Structural basis of the PNRC2-mediated link between mrna surveillance and decapping Structure 2012 20 2025 2037 23085078
  101. [103]Flury V. Restuccia U. Bachi A. Mühlemann O. Characterization of phosphorylation- and RNA-dependent UPF1 interactors by quantitative proteomics J. Proteome Res. 2014 13 3038 3053 24762188
  102. [104]Fairman-Williams M.E. Guenther U.-P. Jankowsky E. SF1 and SF2 helicases: family matters Curr. Opin. Struct. Biol. 2010 20 313 324 20456941 PMC2916977
  103. [105]Woychik N.A. Liao S.M. Kolodziej P.A. Young R.A. Subunits shared by eukaryotic nuclear RNA polymerases Genes Dev. 1990 4 313 323 2186966
  104. [106]Anastasaki C. Longman D. Capper A. Patton E.E. Cáceres J.F. Dhx34 and Nbas function in the NMD pathway and are required for embryonic development in zebrafish Nucleic Acids Res. 2011 39 3686 3694 21227923 PMC3089463
  105. [107]Wimmer K. Zhu X.X. Lamb B.J. Kuick R. Ambros P.F. Kovar H. Thoraval D. Motyka S. Alberts J.R. Hanash S.M. Co-amplification of a novel gene, NAG, with the N-myc gene in neuroblastoma Oncogene 1999 18 233 238 9926938
  106. [108]Scott D.K. Board J.R. Lu X. Pearson A.D. Kenyon R.M. Lunec J. The neuroblastoma amplified gene, NAG: genomic structure and characterisation of the 7.3 kb transcript predominantly expressed in neuroblastoma Gene 2003 307 1 11 12706883
  107. [109]Aoki T. Ichimura S. Itoh A. Kuramoto M. Shinkawa T. Isobe T. Tagaya M. Identification of the neuroblastoma-amplified gene product as a component of the syntaxin 18 complex implicated in Golgi-to-endoplasmic reticulum retrograde transport Mol. Biol. Cell 2009 20 2639 2649 19369418 PMC2688544
  108. [110]Maksimova N. Hara K. Nikolaeva I. Chun-Feng T. Usui T. Takagi M. Nishihira Y. Miyashita A. Fujiwara H. Oyama T. Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger-Huët anomaly J. Med. Genet. 2010 47 538 548 20577004 PMC2921285
  109. [111]Garcia Segarra N. Ballhausen D. Crawford H. Perreau M. Campos-Xavier B. van Spaendonck-Zwarts K. Vermeer C. Russo M. Zambelli P.-Y. Stevenson B. NBAS mutations cause a multisystem disorder involving bone, connective tissue, liver, immune system, and retina Am. J. Med. Genet. A 2015 167A 2902 2912 26286438
  110. [112]Haack T.B. Staufner C. Köpke M.G. Straub B.K. Kölker S. Thiel C. Freisinger P. Baric I. McKiernan P.J. Dikow N. Biallelic mutations in NBAS cause recurrent acute liver failure with onset in infancy Am. J. Hum. Genet. 2015 97 163 169 26073778 PMC4572578
  111. [113]Kamath R.S. Fraser A.G. Dong Y. Poulin G. Durbin R. Gotta M. Kanapin A. Le Bot N. Moreno S. Sohrmann M. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi Nature 2003 421 231 237 12529635
  112. [114]Rual J.-F. Ceron J. Koreth J. Hao T. Nicot A.-S. Hirozane-Kishikawa T. Vandenhaute J. Orkin S.H. Hill D.E. van den Heuvel S. Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based RNAi library Genome Res. 2004 14 2162 2168 15489339 PMC528933
  113. [115]Casadio A. Longman D. Hug N. Delavaine L. Vallejos Baier R. Alonso C.R. Cáceres J.F. Identification and characterization of novel factors that act in the nonsense-mediated mRNA decay pathway in nematodes, flies and mammals EMBO Rep. 2015 16 71 78 25452588 PMC4304730
  114. [116]Saveanu C. Bienvenu D. Namane A. Gleizes P.E. Gas N. Jacquier A. Fromont-Racine M. Nog2p, a putative GTPase associated with pre-60S subunits and required for late 60S maturation steps EMBO J. 2001 20 6475 6484 11707418 PMC125736
  115. [117]Shaywitz D.A. Orci L. Ravazzola M. Swaroop A. Kaiser C.A. Human SEC13Rp functions in yeast and is located on transport vesicles budding from the endoplasmic reticulum J. Cell Biol. 1995 128 769 777 7876304 PMC2120388
  116. [118]Huang L. Wilkinson M.F. Regulation of nonsense-mediated mRNA decay Wiley Interdiscip. Rev. 2012 3 807 828 23027648
  117. [119]Lykke-Andersen S. Jensen T.H. Nonsense-mediated mRNA decay: an intricate machinery that shapes transcriptomes Nat. Rev. Mol. Cell Biol. 2015 16 665 677 26397022
  118. [120]Viegas M.H. Gehring N.H. Breit S. Hentze M.W. Kulozik A.E. The abundance of RNPS1, a protein component of the exon junction complex, can determine the variability in efficiency of the Nonsense Mediated Decay pathway Nucleic Acids Res. 2007 35 4542 4551 17586820 PMC1935013
  119. [121]Medghalchi S.M. Frischmeyer P.A. Mendell J.T. Kelly A.G. Lawler A.M. Dietz H.C. Rent1, a trans-effector of nonsense-mediated mRNA decay, is essential for mammalian embryonic viability Hum. Mol. Genet. 2001 10 99 105 11152657
  120. [122]Li T. Shi Y. Wang P. Guachalla L.M. Sun B. Joerss T. Chen Y.-S. Groth M. Krueger A. Platzer M. Smg6/Est1 licenses embryonic stem cell differentiation via nonsense-mediated mRNA decay EMBO J. 2015 34 1630 1647 25770585 PMC4475398
  121. [123]McIlwain D.R. Pan Q. Reilly P.T. Elia A.J. McCracken S. Wakeham A.C. Itie-Youten A. Blencowe B.J. Mak T.W. Smg1 is required for embryogenesis and regulates diverse genes via alternative splicing coupled to nonsense-mediated mRNA decay Proc. Natl. Acad. Sci. U.S.A. 2010 107 12186 12191 20566848 PMC2901484
  122. [124]Varsally W. Brogna S. UPF1 involvement in nuclear functions Biochem. Soc. Trans. 2012 40 778 783 22817733
  123. [125]Azzalin C.M. Lingner J. The human RNA surveillance factor UPF1 is required for S phase progression and genome stability Curr. Biol. 2006 16 433 439 16488880
  124. [126]Kim Y.K. Furic L. Desgroseillers L. Maquat L.E. Mammalian Staufen1 recruits Upf1 to specific mRNA 3′ UTRs so as to elicit mRNA decay Cell 2005 120 195 208 15680326
  125. [127]Park E. Maquat L.E. Staufen-mediated mRNA decay Wiley Interdiscip. Rev. 2013 4 423 435 PMC3711692 23681777
  126. [128]Kaygun H. Marzluff W.F. Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1 Nat. Struct. Mol. Biol. 2005 12 794 800 16086026
  127. [129]Brumbaugh K.M. Otterness D.M. Geisen C. Oliveira V. Brognard J. Li X. Lejeune F. Tibbetts R.S. Maquat L.E. Abraham R.T. The mRNA surveillance protein hSMG-1 functions in genotoxic stress response pathways in mammalian cells Mol. Cell 2004 14 585 598 15175154
  128. [130]Metzstein M.M. Krasnow M.A. Functions of the nonsense-mediated mRNA decay pathway in Drosophila development PLoS Genet. 2006 2 e180 17196039 PMC1756896
  129. [131]Avery P. Vicente-Crespo M. Francis D. Nashchekina O. Alonso C.R. Palacios I.M. Drosophila Upf1 and Upf2 loss of function inhibits cell growth and causes animal death in a Upf3-independent manner RNA 2011 17 624 638 21317294 PMC3062174
  130. [132]Gardner L.B. Nonsense-mediated RNA decay regulation by cellular stress: implications for tumorigenesis Mol. Cancer Res. 2010 8 295 308 20179151 PMC2841721
  131. [133]Karam R. Wengrod J. Gardner L.B. Wilkinson M.F. Regulation of nonsense-mediated mRNA decay: implications for physiology and disease Biochim. Biophys. Acta 2013 1829 624 633 23500037 PMC3660545
  132. [134]Wang D. Zavadil J. Martin L. Parisi F. Friedman E. Levy D. Harding H. Ron D. Gardner L.B. Inhibition of nonsense-mediated RNA decay by the tumor microenvironment promotes tumorigenesis Mol. Cell. Biol. 2011 31 3670 3680 21730287 PMC3165546
  133. [135]Gardner L.B. Hypoxic inhibition of nonsense-mediated RNA decay regulates gene expression and the integrated stress response Mol. Cell. Biol. 2008 28 3729 3741 18362164 PMC2423288
  134. [136]Karam R. Lou C.-H. Kroeger H. Huang L. Lin J.H. Wilkinson M.F. The unfolded protein response is shaped by the NMD pathway EMBO Rep. 2015 16 599 609 25807986 PMC4428047
  135. [137]Sakaki K. Yoshina S. Shen X. Han J. DeSantis M.R. Xiong M. Mitani S. Kaufman R.J. RNA surveillance is required for endoplasmic reticulum homeostasis Proc. Natl. Acad. Sci. U.S.A. 2012 109 8079 8084 22562797 PMC3361423
  136. [138]Oren Y.S. McClure M.L. Rowe S.M. Sorscher E.J. Bester A.C. Manor M. Kerem E. Rivlin J. Zahdeh F. Mann M. The unfolded protein response affects readthrough of premature termination codons EMBO Mol. Med. 2014 6 685 701 24705877 PMC4023889
  137. [139]Wengrod J. Martin L. Wang D. Frischmeyer-Guerrerio P. Dietz H.C. Gardner L.B. Inhibition of nonsense-mediated RNA decay activates autophagy Mol. Cell. Biol. 2013 33 2128 2135 23508110 PMC3648072
  138. [141]Belew A.T. Meskauskas A. Musalgaonkar S. Advani V.M. Sulima S.O. Kasprzak W.K. Shapiro B.A. Dinman J.D. Ribosomal frameshifting in the CCR5 mRNA is regulated by miRNAs and the NMD pathway Nature 2014 512 265 269 25043019 PMC4369343
  139. [142]Pastor F. Kolonias D. Giangrande P.H. Gilboa E. Induction of tumour immunity by targeted inhibition of nonsense-mediated mRNA decay Nature 2010 465 227 230 20463739 PMC3107067
  140. [143]Nickless A. Jackson E. Marasa J. Nugent P. Mercer R.W. Piwnica-Worms D. You Z. Intracellular calcium regulates nonsense-mediated mRNA decay Nat. Med. 2014 20 961 966 25064126 PMC4126864
  141. [144]Riehs-Kearnan N. Gloggnitzer J. Dekrout B. Jonak C. Riha K. Aberrant growth and lethality of Arabidopsis deficient in nonsense-mediated RNA decay factors is caused by autoimmune-like response Nucleic Acids Res. 2012 40 5615 5624 22379136 PMC3384318
  142. [145]Gloggnitzer J. Akimcheva S. Srinivasan A. Kusenda B. Riehs N. Stampfl H. Bautor J. Dekrout B. Jonak C. Jiménez-Gómez J.M. Nonsense-mediated mRNA decay modulates immune receptor levels to regulate plant antibacterial defense Cell Host Microbe 2014 16 376 390 25211079
  143. [146]Rigby R.E. Rehwinkel J. RNA degradation in antiviral immunity and autoimmunity Trends Immunol. 2015 36 179 188 25709093 PMC4358841
  144. [147]Balistreri G. Horvath P. Schweingruber C. Zünd D. McInerney G. Merits A. Mühlemann O. Azzalin C. Helenius A. The host nonsense-mediated mRNA decay pathway restricts mammalian RNA virus replication Cell Host Microbe 2014 16 403 411 25211080
  145. [148]Weil J.E. Beemon K.L. A 3′ UTR sequence stabilizes termination codons in the unspliced RNA of Rous sarcoma virus RNA 2006 12 102 110 16301601 PMC1370890
  146. [149]Quek B.L. Beemon K. Retroviral strategy to stabilize viral RNA Curr. Opin. Microbiol. 2014 18 78 82 24632073 PMC4020189
  147. [150]Mocquet V. Neusiedler J. Rende F. Cluet D. Robin J.-P. Terme J.-M. Duc Dodon M. Wittmann J. Morris C. Le Hir H. The human T-lymphotropic virus type 1 tax protein inhibits nonsense-mediated mRNA decay by interacting with INT6/EIF3E and UPF1 J. Virol. 2012 86 7530 7543 22553336 PMC3416306
  148. [151]Nakano K. Ando T. Yamagishi M. Yokoyama K. Ishida T. Ohsugi T. Tanaka Y. Brighty D.W. Watanabe T. Viral interference with host mRNA surveillance, the nonsense-mediated mRNA decay (NMD) pathway, through a new function of HTLV-1 Rex: implications for retroviral replication Microbes Infect. 2013 15 491 505 23541980
  149. [152]Garcia D. Garcia S. Voinnet O. Nonsense-mediated decay serves as a general viral restriction mechanism in plants Cell Host Microbe 2014 16 391 402 25155460 PMC7185767
  150. [153]Popp M.W. Maquat L.E. Attenuation of nonsense-mediated mRNA decay facilitates the response to chemotherapeutics Nat. Commun. 2015 6 6632 25808464 PMC4375787
  151. [154]Jia J. Furlan A. Gonzalez-Hilarion S. Leroy C. Gruenert D.C. Tulasne D. Lejeune F. Caspases shutdown nonsense-mediated mRNA decay during apoptosis Cell Death Differ. 2015 22 1754 1763 25744026 PMC4648321
  152. [155]Feng Q. Snider L. Jagannathan S. Tawil R. van der Maarel S.M. Tapscott S.J. Bradley R.K. A feedback loop between nonsense-mediated decay and the retrogene DUX4 in facioscapulohumeral muscular dystrophy Elife 2015 4 e04996 PMC4383350 25564732
  153. [156]Bhuvanagiri M. Lewis J. Putzker K. Becker J.P. Leicht S. Krijgsveld J. Batra R. Turnwald B. Jovanovic B. Hauer C. 5-azacytidine inhibits nonsense-mediated decay in a MYC-dependent fashion EMBO Mol. Med. 2014 6 1593 1609 25319547 PMC4287977
  154. [157]Wang D. Wengrod J. Gardner L.B. Overexpression of the c-myc oncogene inhibits nonsense-mediated RNA decay in B lymphocytes J. Biol. Chem. 2011 286 40038 40043 21969377 PMC3220527
  155. [158]Durand S. Cougot N. Mahuteau-Betzer F. Nguyen C.-H. Grierson D.S. Bertrand E. Tazi J. Lejeune F. Inhibition of nonsense-mediated mRNA decay (NMD) by a new chemical molecule reveals the dynamic of NMD factors in P-bodies J. Cell Biol. 2007 178 1145 1160 17893241 PMC2064650
  156. [159]Martin L. Grigoryan A. Wang D. Wang J. Breda L. Rivella S. Cardozo T. Gardner L.B. Identification and characterization of small molecules that inhibit nonsense-mediated RNA decay and suppress nonsense p53 mutations Cancer Res. 2014 74 3104 3113 24662918 PMC4040335
  157. [160]Dang Y. Low W.-K. Xu J. Gehring N.H. Dietz H.C. Romo D. Liu J.O. Inhibition of nonsense-mediated mRNA decay by the natural product pateamine A through eukaryotic initiation factor 4AIII J. Biol. Chem. 2009 284 23613 23621 19570977 PMC2749136
  158. [161]Feng D. Su R.-C. Zou L. Triggs-Raine B. Huang S. Xie J. Increase of a group of PTC(+) transcripts by curcumin through inhibition of the NMD pathway Biochim. Biophys. Acta 2015 1849 1104 1115 25934542
  159. [162]Gopalsamy A. Bennett E.M. Shi M. Zhang W.-G. Bard J. Yu K. Identification of pyrimidine derivatives as hSMG-1 inhibitors Bioorg. Med. Chem. Lett. 2012 22 6636 6641 23021994
  160. [163]Keeling K.M. Wang D. Conard S.E. Bedwell D.M. Suppression of premature termination codons as a therapeutic approach Crit. Rev. Biochem. Mol. Biol. 2012 47 444 463 22672057 PMC3432268
  161. [164]Keeling K.M. Xue X. Gunn G. Bedwell D.M. Therapeutics based on stop codon readthrough Annu. Rev. Genomics Hum. Genet. 2014 15 371 394 24773318 PMC5304456
  162. [165]Nomakuchi T.T. Rigo F. Aznarez I. Krainer A.R. Antisense oligonucleotide-directed inhibition of nonsense-mediated mRNA decay Nat. Biotechnol. 2015 10.1038/nbt.3427 PMC4744113 26655495 · DOI

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Authors
Hug, N., Longman, D., & Cáceres, J. F.
Affiliations
Western General Hospital (GB)
Corresponding author
Cáceres, Javier F.
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2016-01-14
Volume
44
Issue
4
Pages
1483-1495
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkw010
PMC
PMC4770240
OpenAlex
W2234931430
Cited by
535
References
3
Citations by year
2026: 37 · 2025: 35 · 2024: 58 · 2023: 60 · 2022: 41 · 2021: 65 · 2020: 62 · 2019: 63 · 2018: 47 · 2017: 47 · 2016: 19
FWCI
5.31
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (09518/Z/11/Z, 095518)
  • University of Sussex
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
nonsense-mediated mRNA decay, premature stop codon, RNA helicase, mRNA degradation, trans-acting factors, gene expression regulation
MeSH terms
Gene Expression Regulation, Humans, RNA, Messenger, Codon, Nonsense, RNA Helicases, RNA Stability, Metabolic Networks and Pathways, Nonsense Mediated mRNA Decay

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