Silencing the Transcriptome's Dark Matter: Mechanisms for Suppressing Translation of Intergenic Transcripts

Molecular Cell

Volumn 22, Issue 3, 2006, Pages 309-316

  Bickel, Kellie S ^a   Morris, David R ^a  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RNA; TRANSCRIPTOME;

CHROMATIN STRUCTURE; CYTOSOL; GENE FUNCTION; GENE SILENCING; GENOME; HUMAN; MEDICAL RESEARCH; NONHUMAN; PROTEIN DEGRADATION; REVIEW; TRANSACTIVATION; TRANSCRIPTION INITIATION;

ANIMALS; DNA, INTERGENIC; GENE SILENCING; PROTEIN BIOSYNTHESIS; RNA, MESSENGER; RNA, UNTRANSLATED; TRANSCRIPTION, GENETIC;

EUKARYOTA;

EID: 33646159513     PISSN: 10972765     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.molcel.2006.04.010     Document Type: Review

References (117)

1. Andolfatto P. Adaptive evolution of non-coding DNA in Drosophila. Nature 437 (2005) 1149-1152
2. Araki Y., Takahashi S., Kobayashi T., Kajiho H., Hoshino S., and Katada T. Ski7p G protein interacts with the exosome and the Ski complex for 3′-to-5′ mRNA decay in yeast. EMBO J. 20 (2001) 4684-4693
3. Arava Y., Wang Y., Storey J.D., Liu C.L., Brown P.O., and Herschlag D. Genome-wide analysis of mRNA translation profiles in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 100 (2003) 3889-3894
4. Bass B.L., and Weintraub H. An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell 55 (1988) 1089-1098
5. Bejerano G., Pheasant M., Makunin I., Stephen S., Kent W.J., Mattick J.S., and Haussler D. Ultraconserved elements in the human genome. Science 304 (2004) 1321-1325
6. Bernstein E., Caudy A.A., Hammond S.M., and Hannon G.J. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409 (2001) 363-366
7. Bertone P., Stolc V., Royce T.E., Rozowsky J.S., Urban A.E., Zhu X., Rinn J.L., Tongprasit W., Samanta M., Weissman S., et al. Global identification of human transcribed sequences with genome tiling arrays. Science 306 (2004) 2242-2246
8. Bolland D.J., Wood A.L., Johnston C.M., Bunting S.F., Morgan G., Chakalova L., Fraser P.J., and Corcoran A.E. Antisense intergenic transcription in V(D)J recombination. Nat. Immunol. 5 (2004) 630-637
9. Bousquet-Antonelli C., Presutti C., and Tollervey D. Identification of a regulated pathway for nuclear pre-mRNA turnover. Cell 102 (2000) 765-775
10. Brengues M., Teixeira D., and Parker R. Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies. Science 310 (2005) 486-489
11. Brown C.E., and Sachs A.B. Poly(A) tail length control in Saccharomyces cerevisiae occurs by message-specific deadenylation. Mol. Cell. Biol. 18 (1998) 6548-6559
12. Brown C.Y., Mize G.J., Pineda M., George D.L., and Morris D.R. Role of two upstream open reading frames in the translational control of oncogene mdm2. Oncogene 18 (1999) 5631-5637
13. Burkard K.T., and Butler J.S. A nuclear 3′-5′ exonuclease involved in mRNA degradation interacts with Poly(A) polymerase and the hnRNA protein Npl3p. Mol. Cell. Biol. 20 (2000) 604-616
14. Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., et al. The transcriptional landscape of the mammalian genome. Science 309 (2005) 1559-1563
15. Casolari J.M., and Silver P.A. Guardian at the gate: preventing unspliced pre-mRNA export. Trends Cell Biol. 14 (2004) 222-225
16. Chen C.Y., Gherzi R., Ong S.E., Chan E.L., Raijmakers R., Pruijn G.J., Stoecklin G., Moroni C., Mann M., and Karin M. AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 107 (2001) 451-464
17. Chen J., Sun M., Kent W.J., Huang X., Xie H., Wang W., Zhou G., Shi R.Z., and Rowley J.D. Over 20% of human transcripts might form sense-antisense pairs. Nucleic Acids Res. 32 (2004) 4812-4820
18. Cheng J., Kapranov P., Drenkow J., Dike S., Brubaker S., Patel S., Long J., Stern D., Tammana H., Helt G., et al. Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science 308 (2005) 1149-1154
19. Coller J., and Parker R. General translational repression by activators of mRNA decapping. Cell 122 (2005) 875-886
20. Conti E., and Izaurralde E. Nonsense-mediated mRNA decay: molecular insights and mechanistic variations across species. Curr. Opin. Cell Biol. 17 (2005) 316-325
21. Danin-Kreiselman N., Lee C.Y., and Chanfreau G. RNAse III-mediated degradation of unspliced pre-mRNAs and lariat introns. Mol. Cell 11 (2003) 1279-1289
22. Darzacq X., Singer R.H., and Shav-Tal Y. Dynamics of transcription and mRNA export. Curr. Opin. Cell Biol. 17 (2005) 332-339
23. Davis C.A., and Ares Jr. M. Accumulation of unstable promoter-associated transcripts upon loss of the nuclear exosome subunit Rrp6p in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 103 (2006) 3262-3267
24. Doma M.K., and Parker R. Endonucleolytic cleavage of eukaryotic mRNAs with stalls in translation elongation. Nature 440 (2006) 561-564
25. Dunckley T., and Parker R. The DCP2 protein is required for mRNA decapping in Saccharomyces cerevisiae and contains a functional MutT motif. EMBO J. 18 (1999) 5411-5422
26. Dunn E.F., Hammell C.M., Hodge C.A., and Cole C.N. Yeast poly(A)-binding protein, Pab1, and PAN, a poly(A) nuclease complex recruited by Pab1, connect mRNA biogenesis to export. Genes Dev. 19 (2005) 90-103
27. Dziembowski A., Ventura A.P., Rutz B., Caspary F., Faux C., Halgand F., Laprevote O., and Seraphin B. Proteomic analysis identifies a new complex required for nuclear pre-mRNA retention and splicing. EMBO J. 23 (2004) 4847-4856
28. Egecioglu D.E., Henras A.K., and Chanfreau G.F. Contributions of Trf4p- and Trf5p-dependent polyadenylation to the processing and degradative functions of the yeast nuclear exosome. RNA 12 (2006) 26-32
29. Fasken M.B., and Corbett A.H. Process or perish: quality control in mRNA biogenesis. Nat. Struct. Mol. Biol. 12 (2005) 482-488
30. Frischmeyer P.A., van Hoof H.A., O'Donnell K., Guerrerio A.L., Parker R., and Dietz H.C. An mRNA surveillance mechanism that eliminates transcripts lacking termination codons. Science 295 (2002) 2258-2261
31. Fukagawa T., Nogami M., Yoshikawa M., Ikeno M., Okazaki T., Takami Y., Nakayama T., and Oshimura M. Dicer is essential for formation of the heterochromatin structure in vertebrate cells. Nat. Cell Biol. 6 (2004) 784-791
32. Gaba A., Jacobson A., and Sachs M.S. Ribosome occupancy of the yeast CPA1 upstream open reading frame termination codon modulates nonsense-mediated mRNA decay. Mol. Cell 20 (2005) 449-460
33. Galy V., Gadal O., Fromont-Racine M., Romano A., Jacquier A., and Nehrbass U. Nuclear retention of unspliced mRNAs in yeast is mediated by perinuclear Mlp1. Cell 116 (2004) 63-73
34. Gebauer F., and Hentze M.W. Molecular mechanisms of translational control. Nat. Rev. Mol. Cell Biol. 5 (2004) 827-835
35. Glickman M.H., and Ciechanover A. The ubitquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol. Rev. 82 (2002) 373-428
36. Goldberg A.L. Protein degradation and protection against misfolded or damaged proteins. Nature 426 (2003) 895-899
37. Harris H. Rapidly labelled ribonucleic acid in the cell nucleus. Nature 198 (1963) 184-185
38. Haussecker D., and Proudfoot N.J. Dicer-dependent turnover of intergenic transcripts from the human beta-globin gene cluster. Mol. Cell. Biol. 25 (2005) 9724-9733
39. Hieronymus H., Yu M.C., and Silver P.A. Genome-wide mRNA surveillance is coupled to mRNA export. Genes Dev. 18 (2004) 2652-2662
40. Hilleren P., McCarthy T., Rosbash M., Parker R., and Jensen T.H. Quality control of mRNA 3′-end processing is linked to the nuclear exosome. Nature 413 (2001) 538-542
41. Hilleren P.J., and Parker R. Cytoplasmic degradation of splice-defective pre-mRNAs and intermediates. Mol. Cell 12 (2003) 1453-1465
42. Hirschman J.E., Durbin K.J., and Winston F. Genetic evidence for promoter competition in Saccharomyces cerevisiae. Mol. Cell. Biol. 8 (1988) 4608-4615
43. Hough B.R., Smith M.J., Britten R.J., and Davidson E.H. Sequence complexity of heterogeneous nuclear RNA in sea urchin embryos. Cell 5 (1975) 291-299
44. Houseley J., and Tollervey D. Yeast Trf5p is a nuclear poly(A) polymerase. EMBO Rep. 7 (2006) 205-211
45. Houssais J.F., and Attardi G. High molecular weight nonribosomal-type nuclear RNA and cytoplasmic messenger RNA in HeLa cells. Proc. Natl. Acad. Sci. USA 56 (1966) 616-623
46. Hsu C.L., and Stevens A. Yeast cells lacking 5′→3′ exoribonuclease 1 contain mRNA species that are poly(A) deficient and partially lack the 5′ cap structure. Mol. Cell. Biol. 13 (1993) 4826-4835
47. Huertas D., Cortes A., Casanova J., and Azorin F. Drosophila DDP1, a multi-KH-domain protein, contributes to centromeric silencing and chromosome segregation. Curr. Biol. 14 (2004) 1611-1620
48. Imanishi T., Itoh T., Suzuki Y., O'Donovan C., Fukuchi S., Koyanagi K.O., Barrero R.A., Tamura T., Yamaguchi-Kabata Y., Tanino M., et al. Integrative annotation of 21,037 human genes validated by full-length cDNA clones. PLoS Biol. 2 (2004) e162 10.1371/journal.pbio.0020162
49. Jin X., Turcott E., Englehardt S., Mize G.J., and Morris D.R. The two upstream open reading frames of oncogene mdm2 have different translational regulatory properties. J. Biol. Chem. 278 (2003) 25716-25721
50. Jing Q., Huang S., Guth S., Zarubin T., Motoyama A., Chen J., Di P.F., Lin S.C., Gram H., and Han J. Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell 120 (2005) 623-634
51. Kadaba S., Krueger A., Trice T., Krecic A.M., Hinnebusch A.G., and Anderson J. Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae. Genes Dev. 18 (2004) 1227-1240
52. Kadaba S., Wang X., and Anderson J.T. Nuclear RNA surveillance in Saccharomyces cerevisiae: Trf4p-dependent polyadenylation of nascent hypomethylated tRNA and an aberrant form of 5S rRNA. RNA 12 (2006) 508-521
53. Kampa D., Cheng J., Kapranov P., Yamanaka M., Brubaker S., Cawley S., Drenkow J., Piccolboni A., Bekiranov S., Helt G., et al. Novel RNAs identified from an in-depth analysis of the transcriptome of human chromosomes 21 and 22. Genome Res. 14 (2004) 331-342
54. Kapranov P., Cawley S.E., Drenkow J., Bekiranov S., Strausberg R.L., Fodor S.P., and Gingeras T.R. Large-scale transcriptional activity in chromosomes 21 and 22. Science 296 (2002) 916-919
55. Katayama S., Tomaru Y., Kasukawa T., Waki K., Nakanishi M., Nakamura M., Nishida H., Yap C.C., Suzuki M., Kawai J., et al. Antisense transcription in the mammalian transcriptome. Science 309 (2005) 1564-1566
56. Kim Y.K., Furic L., Desgroseillers L., and Maquat L.E. Mammalian Staufen1 recruits Upf1 to specific mRNA 3′UTRs so as to elicit mRNA decay. Cell 120 (2005) 195-208
57. Kozak M. Regulation of translation via mRNA structure in prokaryotes and eukaryotes. Gene 361 (2005) 13-37
58. Kumar M., and Carmichael G.G. Nuclear antisense RNA induces extensive adenosine modifications and nuclear retention of target transcripts. Proc. Natl. Acad. Sci. USA 94 (1997) 3542-3547
59. LaCava J., Houseley J., Saveanu C., Petfalski E., Thompson E., Jacquier A., and Tollervey D. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 121 (2005) 713-724
60. LaGrandeur T.E., and Parker R. Isolation and characterization of Dcp1p, the yeast mRNA decapping enzyme. EMBO J. 17 (1998) 1487-1496
61. Lai W.S., Kennington E.A., and Blackshear P.J. Tristetraprolin and its family members can promote the cell-free deadenylation of AU-rich element-containing mRNAs by poly(A) ribonuclease. Mol. Cell. Biol. 23 (2003) 3798-3812
62. Lander E.S., Linton L.M., Birren B., Nusbaum C., Zody M.C., Baldwin J., Devon K., Dewar K., Doyle M., FitzHugh W., et al. Initial sequencing and analysis of the human genome. Nature 409 (2001) 860-921
63. Landry J.R., Mager D.L., and Wilhelm B.T. Complex controls: the role of alternative promoters in mammalian genomes. Trends Genet. 19 (2003) 640-648
64. Law G.L., Bickel K.S., MacKay V.L., and Morris D.R. The under-translated transcriptome reveals widespread translational silencing by alternative 5′ transcript leaders. Genome Biol. 6 (2005) R111
65. Lewis B.P., Burge C.B., and Bartel D.P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120 (2005) 15-20
66. Lim L.P., Lau N.C., Garrett-Engele P., Grimson A., Schelter J.M., Castle J., Bartel D.P., Linsley P.S., and Johnson J.M. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433 (2005) 769-773
67. Lykke-Andersen J., and Wagner E. Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay activation domains in the proteins TTP and BRF-1. Genes Dev. 19 (2005) 351-361
68. MacKay V.L., Li X., Flory M.R., Turcott E., Law G.L., Serikawa K.A., Xu X.L., Lee H., Goodlett D.R., Aebersold R., et al. Gene expression in yeast responding to mating pheromone: analysis by high-resolution translation state analysis and quantitative proteomics. Mol. Cell. Proteomics 3 (2004) 478-489
69. Maquat L.E. Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics. Nat. Rev. Mol. Cell Biol. 5 (2004) 89-99
70. Martens J.A., Wu P.Y., and Winston F. Regulation of an intergenic transcript controls adjacent gene transcription in Saccharomyces cerevisiae. Genes Dev. 19 (2005) 2695-2704
71. Masternak K., Peyraud N., Krawczyk M., Barras E., and Reith W. Chromatin remodeling and extragenic transcription at the MHC class II locus control region. Nat. Immunol. 4 (2003) 132-137
72. Masuyama K., Taniguchi I., Kataoka N., and Ohno M. RNA length defines RNA export pathway. Genes Dev. 18 (2004) 2074-2085
73. Mattick J.S. RNA regulation: a new genetics?. Nat. Rev. Genet. 5 (2004) 316-323
74. Mitchell P., and Tollervey D. Musing on the structural organization of the exosome complex. Nat. Struct. Biol. 7 (2000) 843-846
75. Mitchell P., Petfalski E., Shevchenko A., Mann M., and Tollervey D. The exosome: a conserved eukaryotic RNA processing complex containing multiple 3′→5′ exoribonucleases. Cell 91 (1997) 457-466
76. Moore M.J. From birth to death: the complex lives of eukaryotic mRNAs. Science 309 (2005) 1514-1518
77. Morris D.R., and Geballe A.P. Upstream open reading frames as regulators of mRNA translation. Mol. Cell. Biol. 20 (2000) 8635-8642
78. Morris K.V., Chan S.W., Jacobsen S.E., and Looney D.J. Small interfering RNA-induced transcriptional gene silencing in human cells. Science 305 (2004) 1289-1292
79. Numata K., Kanai A., Saito R., Kondo S., Adachi J., Wilming L.G., Hume D.A., Hayashizaki Y., and Tomita M. Identification of putative noncoding RNAs among the RIKEN mouse full-length cDNA collection. Genome Res. 13 (2003) 1301-1306
80. Pal-Bhadra M., Leibovitch B.A., Gandhi S.G., Rao M., Bhadra U., Birchler J.A., and Elgin S.C. Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303 (2004) 669-672
81. Parker R., and Song H. The enzymes and control of eukaryotic mRNA turnover. Nat. Struct. Mol. Biol. 11 (2004) 121-127
82. Penman S. RNA metabolism in the HeLa cell nucleus. J. Mol. Biol. 17 (1966) 117-130
83. Polson A.G., and Bass B.L. Preferential selection of adenosines for modification by double-stranded RNA adenosine deaminase. EMBO J. 13 (1994) 5701-5711
84. Preiss T., Baron-Benhamou J., Ansorge W., and Hentze M.W. Homodirectional changes in transcriptome composition and mRNA translation induced by rapamycin and heat shock. Nat. Struct. Biol. 10 (2003) 1039-1047
85. Radonjic M., Andrau J.-C., Lijnzaad P., Kemmeren P., Kockelkorn T.T.J.P., van Leenen D., van Berkum N.L., and Holstege F.C.P. Genome-wide analyses reveal RNA polymerase II located upstream of genes poised for rapid response upon S. cerevisiae stationary phase exit. Mol. Cell 18 (2005) 171-183
86. Rinn J.L., Euskirchen G., Bertone P., Martone R., Luscombe N.M., Hartman S., Harrison P.M., Nelson F.K., Miller P., Gerstein M., et al. The transcriptional activity of human Chromosome 22. Genes Dev. 17 (2003) 529-540
87. Rogan D.F., Cousins D.J., Santangelo S., Ioannou P.A., Antoniou M., Lee T.H., and Staynov D.Z. Analysis of intergenic transcription in the human IL-4/IL-13 gene cluster. Proc. Natl. Acad. Sci. USA 101 (2004) 2446-2451
88. Routledge S.J., and Proudfoot N.J. Definition of transcriptional promoters in the human beta globin locus control region. J. Mol. Biol. 323 (2002) 601-611
89. Saguez C., Olesen J.R., and Jensen T.H. Formation of export-competent mRNP: escaping nuclear destruction. Curr. Opin. Cell Biol. 17 (2005) 287-293
90. Schadt E.E., Edwards S.W., GuhaThakurta D., Holder D., Ying L., Svetnik V., Leonardson A., Hart K.W., Russell A., Li G., et al. A comprehensive transcript index of the human genome generated using microarrays and computational approaches. Genome Biol. 5 (2004) R73
91. Schmitt S., Prestel M., and Paro R. Intergenic transcription through a polycomb group response element counteracts silencing. Genes Dev. 19 (2005) 697-708
92. Semon M., and Duret L. Evidence that functional transcription units cover at least half of the human genome. Trends Genet. 20 (2004) 229-232
93. Shalgi R., Lapidot M., Shamir R., and Pilpel Y. A catalog of stability-associated sequence elements in 3′ UTRs of yeast mRNAs. Genome Biol. 6 (2005) R86
94. Sheth U., and Parker R. Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science 300 (2003) 805-808
95. Stoecklin G., Colombi M., Raineri I., Leuenberger S., Mallaun M., Schmidlin M., Gross B., Lu M., Kitamura T., and Moroni C. Functional cloning of BRF1, a regulator of ARE-dependent mRNA turnover. EMBO J. 21 (2002) 4709-4718
96. Stolc V., Gauhar Z., Mason C., Halasz G., van Batenburg M.F., Rifkin S.A., Hua S., Herreman T., Tongprasit W., Barbano P.E., et al. A gene expression map for the euchromatic genome of Drosophila melanogaster. Science 306 (2004) 655-660
97. Tan J.S., Mohandas N., and Conboy J.G. High frequency of alternative first exons in erythroid genes suggests a critical role in regulating gene function. Blood 107 (2005) 2557-2561
98. Teixeira D., Sheth U., Valencia-Sanchez M.A., Brengues M., and Parker R. Processing bodies require RNA for assembly and contain nontranslating mRNAs. RNA 11 (2005) 371-382
99. Valencia-Sanchez M.A., Liu J., Hannon G.J., and Parker R. Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 20 (2006) 515-524
100. Vanacova S., Wolf J., Martin G., Blank D., Dettwiler S., Friedlein A., Langen H., Keith G., and Keller W. A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol. 3 (2005) e189 10.1371/journal.pbio.0030189
101. vanHoof A., Frischmeyer P.A., Dietz H.C., and Parker R. Exosome-mediated recognition and degradation of mRNAs lacking a termination codon. Science 295 (2002) 2262-2264
102. Vasudevan S., and Peltz S.W. Nuclear mRNA surveillance. Curr. Opin. Cell Biol. 15 (2003) 332-337
103. Venter J.C., Adams M.D., Myers E.W., Li P.W., Mural R.J., Sutton G.G., Smith H.O., Yandell M., Evans C.A., Holt R.A., et al. The sequence of the human genome. Science 291 (2001) 1304-1351
104. Volpe T.A., Kidner C., Hall I.M., Teng G., Grewal S.I., and Martienssen R.A. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297 (2002) 1833-1837
105. Wahle E. Poly(A) tail length control is caused by termination of processive synthesis. J. Biol. Chem. 270 (1995) 2800-2808
106. Wang Q., and Carmichael G.G. Effects of length and location on the cellular response to double-stranded RNA. Microbiol. Mol. Biol. Rev. 68 (2004) 432-452
107. Wang Q., Zhang Z., Blackwell K., and Carmichael G.G. Vigilins bind to promiscuously A-to-I-edited RNAs and are involved in the formation of heterochromatin. Curr. Biol. 15 (2005) 384-391
108. Wang Z., Jiao X., Carr-Schmid A., and Kiledjian M. The hDcp2 protein is a mammalian mRNA decapping enzyme. Proc. Natl. Acad. Sci. USA 99 (2002) 12663-12668
109. Warner J.R., Soeiro R., Birnboim H.C., Girard M., and Darnell J.E. Rapidly labeled HeLa cell nuclear RNA. I. Identification by zone sedimentation of a heterogeneous fraction separate from ribosomal precursor RNA. J. Mol. Biol. 19 (1966) 349-361
110. Waterhouse P., Khokha R., and Denhardt D.T. Modulation of translation by the 5′-leader sequence of the messenger RNA encoding murine tissue inhibitor of metalloproteinases. J. Biol. Chem. 265 (1990) 5585-5589
111. Werner A., and Berdal A. Natural antisense transcripts: sound or silence?. Physiol. Genomics 23 (2005) 125-131
112. Willingham A.T., Orth A.P., Batalov S., Peters E.C., Wen B.G., Aza-Blanc P., Hogenesch J.B., and Schultz P.G. A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 309 (2005) 1570-1573
113. Wyers F., Rougemaille M., Badis G., Rousselle J.C., Dufour M.E., Boulay J., Regnault B., Devaux F., Namane A., Seraphin B., et al. Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 121 (2005) 725-737
114. Xie X., Lu J., Kulbokas E.J., Golub T.R., Mootha V., Lindblad-Toh K., Lander E.S., and Kellis M. Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals. Nature 434 (2005) 338-345
115. Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M., Wu H.C., Kim C., Nguyen M., et al. Empirical analysis of transcriptional activity in the Arabidopsis genome. Science 302 (2003) 842-846
116. Yelin R., Dahary D., Sorek R., Levanon E.Y., Goldstein O., Shoshan A., Diber A., Biton S., Tamir Y., Khosravi R., et al. Widespread occurrence of antisense transcription in the human genome. Nat. Biotechnol. 21 (2003) 379-386
117. Zhang Z., and Carmichael G.G. The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs. Cell 106 (2001) 465-475