Regulation of gene expression through production of unstable mRNA isoforms

Biochemical Society Transactions

Volumn 42, Issue 4, 2014, Pages 1196-1205

  Sibley, Christopher R ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Alternative splicing; Alternative splicing coupled nonsense mediated decay (ASNMD); Post transcriptional control; Premature termination codon; Regulated intron retention

Indexed keywords

RNA ISOFORM; MESSENGER RNA;

ALTERNATIVE RNA SPLICING; CONFERENCE PAPER; GENE CONTROL; GENE EXPRESSION; GENETIC DISORDER; HUMAN; INTRON RETENTION; MESSENGER RNA SYNTHESIS; NONSENSE MEDIATED MRNA DECAY; PRIORITY JOURNAL; SPLICEOSOME; ANIMAL; GENETICS; PHYSIOLOGY; RNA STABILITY;

ALTERNATIVE SPLICING; ANIMALS; HUMANS; RNA ISOFORMS; RNA STABILITY; RNA, MESSENGER;

EID: 84905869925     PISSN: 03005127     EISSN: 14708752     Source Type: Journal    
DOI: 10.1042/BST20140102     Document Type: Conference Paper

References (112)

1. Matera, A.G. and Wang, Z. (2014) A day in the life of the spliceosome. Nat. Rev. Mol. Cell Biol. 15, 108-121
2. Ruskin, B., Zamore, P.D. and Green, M.R. (1988) A factor, U2AF, is required for U2 snRNP binding and splicing complex assembly. Cell: 52, 207-219
3. Zamore, P.D. and Green, M.R. (1989) Identification, purification, and biochemical characterization of U2 small nuclear ribonucleoprotein auxiliary factor. Proc. Natl. Acad. Sci. U.S.A. 86, 9243-9247
4. De Conti, L., Baralle, M. and Buratti, E. (2013) Exon and intron definition in pre-mRNA splicing. Wiley Interdiscip. Rev. RNA 4, 49-60
5. Pan, Q., Shai, O., Lee, L.J., Frey, B.J. and Blencowe, B.J. (2008) Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat. Genet. 40, 1413-1415
6. Wang, E.T., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S.F., Schroth, G.P. and Burge, C.B. (2008) Alternative isoform regulation in human tissue transcriptomes. Nature 456, 470-476
7. Tollervey, J.R., Curk, T., Rogelj, B., Briese, M., Cereda, M., Kayikci, M., Konig, J., Hortobagyi, T., Nishimura, A.L., Zupunski, V. et al. (2011) Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat. Neurosci. 14, 452-458
8. Ule, J., Jensen, K.B., Ruggiu, M., Mele, A., Ule, A. and Darnell, R.B. (2003) CLIP identifies Nova-regulated RNA networks in the brain. Science 302, 1212-1215
9. Wang, Z., Kayikci, M., Briese, M., Zarnack, K., Luscombe, N.M., Rot, G., Zupan, B., Curk, T. and Ule, J. (2010) iCLIP predicts the dual splicing effects of TIA-RNA interactions. PLoS Biol 8, e1000530
10. Wang, E.T., Cody, N.A., Jog, S., Biancolella, M., Wang, T.T., Treacy, D.J., Luo, S., Schroth, G.P., Housman, D.E., Reddy, S. et al. (2012) Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins. Cell 150, 710-724
11. Fairbrother, W.G., Yeh, R.F., Sharp, P.A. and Burge, C.B. (2002) Predictive identification of exonic splicing enhancers in human genes. Science 297, 1007-1013
12. Ke, S., Shang, S., Kalachikov, S.M., Morozova, I., Yu, L., Russo, J.J., Ju, J. and Chasin, L.A. (2011) Quantitative evaluation of all hexamers as exonic splicing elements. Genome Res. 21, 1360-1374
13. Busch, A. and Hertel, K.J. (2012) Evolution of SR protein and hnRNP splicing regulatory factors. Wiley Interdiscip. Rev RNA 3, 1-12
14. Zahler, A.M. and Roth, M.B. (1995) Distinct functions of SR proteins in recruitment of U1 small nuclear ribonucleoprotein to alternative 5 splice sites. Proc. Natl. Acad. Sci. U.S.A. 92, 2642-2646
15. Lavigueur, A., La Branche, H., Kornblihtt, A.R. and Chabot, B. (1993) A splicing enhancer in the human fibronectin alternate ED1 exon interacts with SR proteins and stimulates U2 snRNP binding. Genes Dev. 7, 2405-2417
16. Tarn, W.Y. and Steitz, J.A. (1995) Modulation of 5 splice site choice in pre-messenger RNA by two distinct steps. Proc. Natl. Acad. Sci. U.S.A. 92, 2504-2508
17. Roscigno, R.F. and Garcia-Blanco, M.A. (1995) SR proteins escort the U4/U6.U5 tri-snRNP to the spliceosome. RNA 1, 692-706
18. Zarnack, K., Konig, J., Tajnik, M., Martincorena, I., Eustermann, S., Stevant, I., Reyes, A., Anders, S., Luscombe, N.M. and Ule, J. (2013) Direct competition between hnRNP C and U2AF65 protects the transcriptome from the exonization of Alu elements. Cell 152, 453-466
19. Schoenberg, D.R. and Maquat, L.E. (2012) Regulation of cytoplasmic mRNA decay. Nat. Rev. Genet. 13, 246-259
20. Sauliere, J., Murigneux, V., Wang, Z., Marquenet, E., Barbosa, I., Le Tonqueze, O., Audic, Y., Paillard, L., Roest Crollius, H. and Le Hir, H. (2012) CLIP-seq of eIF4AIII reveals transcriptome-wide mapping of the human exon junction complex. Nat. Struct. Mol. Biol. 19, 1124-1131
21. Le Hir, H., Gatfield, D., Izaurralde, E. and Moore, M.J. (2001) The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay. EMBO J. 20, 4987-4997
22. Ishigaki, Y., Li, X., Serin, G. and Maquat, L.E. (2001) Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20. Cell 106, 607-617
23. Lejeune, F., Ishigaki, Y., Li, X. and Maquat, L.E. (2002) The exon junction complex is detected on CBP80-bound but not eIF4E-bound mRNA in mammalian cells: dynamics of mRNP remodeling. EMBO J. 21, 3536-3545
24. Dostie, J. and Dreyfuss, G. (2002) Translation is required to remove Y14 from mRNAs in the cytoplasm. Curr. Biol. 12, 1060-1067
25. Kashima, I., Yamashita, A., Izumi, N., Kataoka, N., Morishita, R., Hoshino, S., Ohno, M., Dreyfuss, G. and Ohno, S. (2006) 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. 20, 355-367
26. Hwang, J., Sato, H., Tang, Y., Matsuda, D. and Maquat, L.E. (2010) UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated mRNA decay at two distinct steps. Mol. Cell 39, 396-409
27. Nagy, E. and Maquat, L.E. (1998) A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance. Trends Biochem. Sci. 23, 198-199
28. Lareau, L.F., Inada, M., Green, R.E., Wengrod, J.C. and Brenner, S.E. (2007) Unproductive splicing of SR genes associated with highly conserved and ultraconserved DNA elements. Nature 446, 926-929
29. Eom, T., Zhang, C., Wang, H., Lay, K., Fak, J., Noebels, J.L. and Darnell, R.B. (2013) NOVA-dependent regulation of cryptic NMD exons controls synaptic protein levels after seizure. Elife 2, e00178
30. Lou, C.H., Shao, A., Shum, E.Y., Espinoza, J.L., Huang, L., Karam, R. and Wilkinson, M.F. (2014) Posttranscriptional control of the stem cell and neurogenic programs by the nonsense-mediated RNA decay pathway. Cell Rep. 6, 748-764
31. Mendell, J.T., Sharifi, N.A., Meyers, J.L., Martinez-Murillo, F. and Dietz, H.C. (2004) Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise. Nat. Genet. 36, 1073-1078
32. Kim, K.M., Cho, H. and Kim, Y.K. (2012) The upstream open reading frame of cyclin-dependent kinase inhibitor 1A mRNA negatively regulates translation of the downstream main open reading frame. Biochem. Biophys. Res. Commun. 424, 469-475
33. Bell, T.J., Miyashiro, K.Y., Sul, J.Y., McCullough, R., Buckley, P.T., Jochems, J., Meaney, D.F., Haydon, P., Cantor, C., Parsons, T.D. and Eberwine, J. (2008) Cytoplasmic BK(Ca) channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons. Proc. Natl. Acad. Sci. U.S.A. 105, 1901-1906
34. Wong, J.J., Ritchie, W., Ebner, O.A., Selbach, M., Wong, J.W., Huang, Y., Gao, D., Pinello, N., Gonzalez, M., Baidya, K. et al. (2013) Orchestrated intron retention regulates normal granulocyte differentiation. Cell 154, 583-595
35. Colak, D., Ji, S.J., Porse, B.T. and Jaffrey, S.R. (2013) Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay. Cell 153, 1252-1265
36. Buhler, M. and Muhlemann, O. (2005) Alternative splicing induced by nonsense mutations in the immunoglobulin mu VDJ exon is independent of truncation of the open reading frame. RNA 11, 139-146
37. Yepiskoposyan, H., Aeschimann, F., Nilsson, D., Okoniewski, M. and Muhlemann, O. (2011) Autoregulation of the nonsense-mediated mRNA decay pathway in human cells. RNA 17, 2108-2118
38. Lewis, B.P., Green, R.E. and Brenner, S.E. (2003) Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans. Proc. Natl. Acad. Sci. U.S.A. 100, 189-192
39. Baek, D. and Green, P. (2005) Sequence conservation, relative isoform frequencies, and nonsense-mediated decay in evolutionarily conserved alternative splicing. Proc. Natl. Acad. Sci. U.S.A. 102, 12813-12818
40. Weischenfeldt, J., Waage, J., Tian, G., Zhao, J., Damgaard, I., Jakobsen, J.S., Kristiansen, K., Krogh, A., Wang, J. and Porse, B.T. (2012) Mammalian tissues defective in nonsense-mediated mRNA decay display highly aberrant splicing patterns. Genome Biol. 13, R35
41. McGlincy, N.J. and Smith, C.W. (2008) Alternative splicing resulting in nonsense-mediated mRNA decay: what is the meaning of nonsense?. Trends Biochem Sci. 33, 385-393
42. Neu-Yilik, G. and Kulozik, A.E. (2008) NMD: multitasking between mRNA surveillance and modulation of gene expression. Adv. Genet. 62, 185-243
43. Green, R.E., Lewis, B.P., Hillman, R.T., Blanchette, M., Lareau, L.F., Garnett, A.T., Rio, D.C. and Brenner, S.E. (2003) Widespread predicted nonsense-mediated mRNA decay of alternatively-spliced transcripts of human normal and disease genes. Bioinformatics 19 (Suppl. 1), i118-i121
44. Boutz, P.L., Stoilov, P., Li, Q., Lin, C.H., Chawla, G., Ostrow, K., Shiue, L., Ares, Jr, M. and Black, D.L. (2007) A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev. 21, 1636-1652
45. Preitner, N., Quan, J. and Flanagan, J.G. (2013) This message will self-destruct: NMD regulates axon guidance. Cell 153, 1185-1187
46. Giorgi, C., Yeo, G.W., Stone, M.E., Katz, D.B., Burge, C., Turrigiano, G. and Moore, M.J. (2007) The EJC factor eIF4AIII modulates synaptic strength and neuronal protein expression. Cell 130, 179-191
47. Sureau, A., Gattoni, R., Dooghe, Y., Stevenin, J. and Soret, J. (2001) SC35 autoregulates its expression by promoting splicing events that destabilize its mRNAs. EMBO J 20, 1785-1796
48. Wollerton, M.C., Gooding, C., Wagner, E.J., Garcia-Blanco, M.A. and Smith, C.W. (2004) Autoregulation of polypyrimidine tract binding protein by alternative splicing leading to nonsense-mediated decay. Mol. Cell 13, 91-100
49. Lejeune, F., Cavaloc, Y. and Stevenin, J. (2001) Alternative splicing of intron 3 of the serine/arginine-rich protein 9G8 gene. Identification of flanking exonic splicing enhancers and involvement of 9G8 as a trans-acting factor. J. Biol. Chem. 276, 7850-7858
50. Kumar, S. and Lopez, A.J. (2005) Negative feedback regulation among SR splicing factors encoded by Rbp1 and Rbp1-like in Drosophila. EMBO J. 24, 2646-2655
51. Ni, J.Z., Grate, L., Donohue, J.P., Preston, C., Nobida, N., O'Brien, G., Shiue, L., Clark, T.A., Blume, J.E. and Ares, Jr, M. (2007) Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay. Genes Dev. 21, 708-718
52. Le Guiner, C., Lejeune, F., Galiana, D., Kister, L., Breathnach, R., Stevenin, J. and Del Gatto-Konczak, F. (2001) TIA-1 and TIAR activate splicing of alternative exons with weak 5 splice sites followed by a U-rich stretch on their own pre-mRNAs. J. Biol. Chem. 276, 40638-40646
53. Rossbach, O., Hung, L.H., Schreiner, S., Grishina, I., Heiner, M., Hui, J. and Bindereif, A. (2009) Auto- and cross-regulation of the hnRNP L proteins by alternative splicing. Mol. Cell Biol. 29, 1442-1451
54. McGlincy, N.J., Tan, L.Y., Paul, N., Zavolan, M., Lilley, K.S. and Smith, C.W. (2010) Expression proteomics of UPF1 knockdown in HeLa cells reveals autoregulation of hnRNP A2/B1 mediated by alternative splicing resulting in nonsense-mediated mRNA decay. BMC Genomics 11, 565
55. Sun, S., Zhang, Z., Fregoso, O. and Krainer, A.R. (2012) Mechanisms of activation and repression by the alternative splicing factors RBFOX1/2. RNA 18, 274-283
56. Rosel-Hillgartner, T.D., Hung, L.H., Khrameeva, E., Le Querrec, P., Gelfand, M.S. and Bindereif, A. (2013) A novel intra-U1 snRNP cross-regulation mechanism: alternative splicing switch links U1C and U1-70K expression. PLoS Genet. 9, e1003856
57. Saltzman, A.L., Pan, Q. and Blencowe, B.J. (2011) Regulation of alternative splicing by the core spliceosomal machinery. Genes Dev. 25, 373-384
58. McIlwain, D.R., Pan, Q., Reilly, P.T., Elia, A.J., McCracken, S., Wakeham, A.C., Itie-Youten, A., Blencowe, B.J. and Mak, T.W. (2010) 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. 107, 12186-12191
59. Hurt, J.A., Robertson, A.D. and Burge, C.B. (2013) Global analyses of UPF1 binding and function reveal expanded scope of nonsense-mediated mRNA decay. Genome Res. 23, 1636-1650
60. Huang, L., Lou, C.H., Chan, W., Shum, E.Y., Shao, A., Stone, E., Karam, R., Song, H.W. and Wilkinson, M.F. (2011) RNA homeostasis governed by cell type-specific and branched feedback loops acting on NMD. Mol. Cell 43, 950-961
61. Valacca, C., Bonomi, S., Buratti, E., Pedrotti, S., Baralle, F.E., Sette, C., Ghigna, C. and Biamonti, G. (2010) Sam68 regulates EMT through alternative splicing-activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene. J. Cell Biol. 191, 87-99
62. Rahman, L., Bliskovski, V., Kaye, F.J. and Zajac-Kaye, M. (2004) Evolutionary conservation of a 2-kb intronic sequence flanking a tissue-specific alternative exon in the PTBP2 gene. Genomics 83, 76-84
63. Makeyev, E.V., Zhang, J., Carrasco, M.A. and Maniatis, T. (2007) The microRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol. Cell 27, 435-448
64. Licatalosi, D.D., Mele, A., Fak, J.J., Ule, J., Kayikci, M., Chi, S.W., Clark, T.A., Schweitzer, A.C., Blume, J.E., Wang, X. et al. (2008) HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature 456, 464-469
65. Ule, J., Stefani, G., Mele, A., Ruggiu, M., Wang, X., Taneri, B., Gaasterland, T., Blencowe, B.J. and Darnell, R.B. (2006) An RNA map predicting Nova-dependent splicing regulation. Nature 444, 580-586
66. Qu, M., Aronica, E., Boer, K., Fallmar, D., Kumlien, E., Nister, M., Wester, K., Ponten, F. and Smits, A. (2009) DLG3/SAP102 protein expression in malformations of cortical development: a study of human epileptic cortex by tissue microarray. Epilepsy Res. 84, 33-41
67. Gurnett, C.A., Veile, R., Zempel, J., Blackburn, L., Lovett, M. and Bowcock, A. (2008) Disruption of sodium bicarbonate transporter SLC4A10 in a patient with complex partial epilepsy and mental retardation. Arch. Neurol. 65, 550-553
68. Sander, T., Toliat, M.R., Heils, A., Leschik, G., Becker, C., Ruschendorf, F., Rohde, K., Mundlos, S. and Nurnberg, P. (2002) Association of the 867Asp variant of the human anion exchanger 3 gene with common subtypes of idiopathic generalized epilepsy. Epilepsy Res. 51, 249-255
69. Dickson, B.J. and Zou, Y. (2010) Navigating intermediate targets: the nervous system midline. Cold Spring Harb. Perspect. Biol. 2, a002055
70. O'Donnell, M., Chance, R.K. and Bashaw, G.J. (2009) Axon growth and guidance: receptor regulation and signal transduction. Annu. Rev. Neurosci. 32, 383-412
71. Chen, Z., Gore, B.B., Long, H., Ma, L. and Tessier-Lavigne, M. (2008) Alternative splicing of the Robo3 axon guidance receptor governs the midline switch from attraction to repulsion. Neuron 58, 325-332
72. Jangi, M., Boutz, P.L., Paul, P. and Sharp, P.A. (2014) Rbfox2 controls autoregulation in RNA-binding protein networks. Genes Dev. 28, 637-651
73. Lestas, I., Vinnicombe, G. and Paulsson, J. (2010) Fundamental limits on the suppression of molecular fluctuations. Nature 467, 174-178
74. Gehring, N.H., Kunz, J.B., Neu-Yilik, G., Breit, S., Viegas, M.H., Hentze, M.W. and Kulozik, A.E. (2005) Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements. Mol. Cell 20, 65-75
75. Chan, W.K., Huang, L., Gudikote, J.P., Chang, Y.F., Imam, J.S., MacLean, II, J.A. and Wilkinson, M.F. (2007) An alternative branch of the nonsense-mediated decay pathway. EMBO J. 26, 1820-1830
76. Galante, P.A., Sakabe, N.J., Kirschbaum-Slager, N. and de Souza, S.J. (2004) Detection and evaluation of intron retention events in the human transcriptome. RNA 10, 757-765
77. Calvanese, V., Mallya, M., Campbell, R.D. and Aguado, B. (2008) Regulation of expression of two LY-6 family genes by intron retention and transcription induced chimerism. BMC Mol. Biol. 9, 81
78. Buckley, P.T., Lee, M.T., Sul, J.Y., Miyashiro, K.Y., Bell, T.J., Fisher, S.A., Kim, J. and Eberwine, J. (2011) Cytoplasmic intron sequence-retaining transcripts can be dendritically targeted via ID element retrotransposons. Neuron 69, 877-884
79. Yap, K., Lim, Z.Q., Khandelia, P., Friedman, B. and Makeyev, E.V. (2012) Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention. Genes Dev. 26, 1209-1223
80. Sakabe, N.J. and de Souza, S.J. (2007) Sequence features responsible for intron retention in human. BMC Genomics 8, 59
81. Amit, M., Donyo, M., Hollander, D., Goren, A., Kim, E., Gelfman, S., Lev-Maor, G., Burstein, D., Schwartz, S., Postolsky, B.G. et al. (2012) Differential GC content between exons and introns establishes distinct strategies of splice-site recognition. Cell Rep. 1, 543-556
82. Roy, D., Bhanja Chowdhury, J. and Ghosh, S. (2013) Polypyrimidine tract binding protein (PTB) associates with intronic and exonic domains to squelch nuclear export of unspliced RNA. FEBS Lett. 587, 3802-3807
83. Takemura, R., Takeiwa, T., Taniguchi, I., McCloskey, A. and Ohno, M. (2011) Multiple factors in the early splicing complex are involved in the nuclear retention of pre-mRNAs in mammalian cells. Genes Cells 16, 1035-1049
84. Ge, Y. and Porse, B.T. (2013) The functional consequences of intron retention: alternative splicing coupled to NMD as a regulator of gene expression. Bioessays 36, 236-243
85. Linde, L. and Kerem, B. (2011) Nonsense-mediated mRNA decay and cystic fibrosis. Methods Mol. Biol. 741, 137-154
86. Buratti, E., Chivers, M., Hwang, G. and Vorechovsky, I. (2011) DBASS3 and DBASS5: databases of aberrant 3- and 5 -splice sites. Nucleic Acids Res. 39, D86-D91
87. Bidou, L., Allamand, V., Rousset, J.P. and Namy, O. (2012) Sense from nonsense: therapies for premature stop codon diseases. Trends Mol. Med. 18, 679-688
88. Qadah, T., Finlayson, J., Newbound, C., Pell, N., Pascoe, M., Greenwood, L., Holmes, P., Grey, D., Beilby, J. and Ghassemifar, R. (2012) Molecular and cellular characterization of a new -thalassemia mutation (HBA2:c.94A>C) generating an alternative splice site and a premature stop codon. Hemoglobin 36, 244-252
89. Hall, G.W. and Thein, S. (1994) Nonsense codon mutations in the terminal exon of the β-globin gene are not associated with a reduction in β-mRNA accumulation: a mechanism for the phenotype of dominant β-thalassemia. Blood 83, 2031-2037
90. Rosenfeld, P.J., Cowley, G.S., McGee, T.L., Sandberg, M.A., Berson, E.L. and Dryja, T.P. (1992) A null mutation in the rhodopsin gene causes rod photoreceptor dysfunction and autosomal recessive retinitis pigmentosa. Nat. Genet. 1, 209-213
91. Pagani, F., Buratti, E., Stuani, C., Bendix, R., Dork, T. and Baralle, F.E. (2002) A new type of mutation causes a splicing defect in ATM. Nat. Genet. 30, 426-429
92. Parsons, D.W., McAndrew, P.E., Monani, U.R., Mendell, J.R., Burghes, A.H. and Prior, T.W. (1996) An 11 base pair duplication in exon 6 of the SMN gene produces a type I spinal muscular atrophy (SMA) phenotype: further evidence for SMN as the primary SMA-determining gene. Hum. Mol. Genet. 5, 1727-1732
93. Perrin-Vidoz, L., Sinilnikova, O.M., Stoppa-Lyonnet, D., Lenoir, G.M. and Mazoyer, S. (2002) The nonsense-mediated mRNA decay pathway triggers degradation of most BRCA1 mRNAs bearing premature termination codons. Hum. Mol. Genet. 11, 2805-2814
94. Holbrook, J.A., Neu-Yilik, G., Hentze, M.W. and Kulozik, A.E. (2004) Nonsense-mediated decay approaches the clinic. Nat. Genet. 36, 801-808
95. Wolf, M., Edgren, H., Muggerud, A., Kilpinen, S., Huusko, P., Sorlie, T., Mousses, S. and Kallioniemi, O. (2005) NMD microarray analysis for rapid genome-wide screen of mutated genes in cancer. Cell. Oncol. 27, 169-173
96. Karam, R., Carvalho, J., Bruno, I., Graziadio, C., Senz, J., Huntsman, D., Carneiro, F., Seruca, R., Wilkinson, M.F. and Oliveira, C. (2008) The NMD mRNA surveillance pathway downregulates aberrant E-cadherin transcripts in gastric cancer cells and in CDH1 mutation carriers. Oncogene 27, 4255-4260
97. Peltz, S.W., Welch, E.M., Jacobson, A., Trotta, C.R., Naryshkin, N., Sweeney, H.L. and Bedwell, D.M. (2009) Nonsense suppression activity of PTC124 (ataluren). Proc. Natl. Acad. Sci. U.S.A. 106, E64
98. Welch, E.M., Barton, E.R., Zhuo, J., Tomizawa, Y., Friesen, W.J., Trifillis, P., Paushkin, S., Patel, M., Trotta, C.R., Hwang, S. et al. (2007) PTC124 targets genetic disorders caused by nonsense mutations. Nature 447, 87-91
99. Goodier, J.L. and Mayer, J. (2009) PTC124 for cystic fibrosis. Lancet 373, 1426
100. McElroy, S.P., Nomura, T., Torrie, L.S., Warbrick, E., Gartner, U., Wood, G. and McLean, W.H. (2013) A lack of premature termination codon read-through efficacy of PTC124 (Ataluren) in a diverse array of reporter assays. PLoS Biol 11, e1001593
101. Rogelj, B., Easton, L.E., Bogu, G.K., Stanton, L.W., Rot, G., Curk, T., Zupan, B., Sugimoto, Y., Modic, M., Haberman, N. et al. (2012) Widespread binding of FUS along nascent RNA regulates alternative splicing in the brain. Sci. Rep. 2, 603
102. Zhou, Y., Liu, S., Liu, G., Ozturk, A. and Hicks, G.G. (2013) ALS-associated FUS mutations result in compromised FUS alternative splicing and autoregulation. PLoS Genet. 9, e1003895
103. Ayala, Y.M., De Conti, L., Avendano-Vazquez, S.E., Dhir, A., Romano, M., D'Ambrogio, A., Tollervey, J., Ule, J., Baralle, M., Buratti, E. and Baralle, F.E. (2011) TDP-43 regulates its mRNA levels through a negative feedback loop. EMBO J. 30, 277-288
104. Buratti, E. and Baralle, F.E. (2011) TDP-43: new aspects of autoregulation mechanisms in RNA binding proteins and their connection with human disease. FEBS J. 278, 3530-3538
105. Tarpey, P.S., Raymond, F.L., Nguyen, L.S., Rodriguez, J., Hackett, A., Vandeleur, L., Smith, R., Shoubridge, C., Edkins, S., Stevens, C. et al. (2007) Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation. Nat. Genet. 39, 1127-1133
106. Laumonnier, F., Shoubridge, C., Antar, C., Nguyen, L.S., Van Esch, H., Kleefstra, T., Briault, S., Fryns, J.P., Hamel, B., Chelly, J. et al. (2010) Mutations of the UPF3B gene, which encodes a protein widely expressed in neurons, are associated with nonspecific mental retardation with or without autism. Mol. Psychiatry 15, 767-776
107. Addington, A.M., Gauthier, J., Piton, A., Hamdan, F.F., Raymond, A., Gogtay, N., Miller, R., Tossell, J., Bakalar, J., Inoff-Germain, G. et al. (2011) A novel frameshift mutation in UPF3B identified in brothers affected with childhood onset schizophrenia and autism spectrum disorders. Mol. Psychiatry 16, 238-239
108. Nguyen, L.S., Jolly, L., Shoubridge, C., Chan, W.K., Huang, L., Laumonnier, F., Raynaud, M., Hackett, A., Field, M., Rodriguez, J. et al. (2012) Transcriptome profiling of UPF3B/NMD-deficient lymphoblastoid cells from patients with various forms of intellectual disability. Mol. Psychiatry 17, 1103-1115
109. Kapustin, Y., Chan, E., Sarkar, R., Wong, F., Vorechovsky, I., Winston, R.M., Tatusova, T. and Dibb, N.J. (2011) Cryptic splice sites and split genes. Nucleic Acids Res. 39, 5837-5844
110. Brown, J.B., Boley, N., Eisman, R., May, G.E., Stoiber, M.H., Duff, M.O., Booth, B.W., Wen, J., Park, S., Suzuki, A.M. et al. (2014) Diversity and dynamics of the Drosophila transcriptome. Nature, doi:10.1038/nature12962
111. Boley, N., Stoiber, M.H., Booth, B.W., Wan, K.H., Hoskins, R.A., Bickel, P.J., Celniker, S.E. and Brown, J.B. 2014 Genome-guided transcript assembly by integrative analysis of RNA sequence data. Nat. Biotechnol. 32, 341-346
112. Modic, M., Ule, J. and Sibley, C.R. (2013) CLIPing the brain: studies of protein-RNA interactions important for neurodegenerative disorders. Mol. Cell. Neurosci. 56, 429-435