RNA Exosome Regulates AID DNA Mutator Activity in the B Cell Genome

Advances in Immunology

Volumn 127, Issue , 2015, Pages 257-308

  Pefanis, Evangelos ^a,b   Basu, Uttiya ^a  

^a Department of Microbiology and Immunology College of Physicians and Surgeons Columbia University ^*  (United States)

^b AB)   (United States)

Author keywords

Activation induced cytidine deaminase; Antisense RNA; B lymphocytes; Noncoding RNA; RNA exosome; Somatic hypermutation; Transcription termination

Indexed keywords

ACTIVATION INDUCED CYTIDINE DEAMINASE; CYTIDINE; DNA; IMMUNOGLOBULIN; RNA; SINGLE STRANDED DNA; TRANSCRIPTOME; CYTIDINE DEAMINASE; EXOSOME MULTIENZYME RIBONUCLEASE COMPLEX;

B LYMPHOCYTE; CATALYSIS; CELL FUNCTION; CELL STRUCTURE; CHROMATIN; ENZYME ACTIVITY; EXOSOME; GENE LOCUS; GENETIC ASSOCIATION; GENOME; GENOMIC INSTABILITY; HUMAN; NONHUMAN; PRIORITY JOURNAL; RNA DEGRADATION; SOMATIC HYPERMUTATION; TRANSCRIPTION TERMINATION; ANIMAL; GENETIC TRANSCRIPTION; METABOLISM; MUTAGENESIS;

ANIMALS; B-LYMPHOCYTES; CYTIDINE DEAMINASE; EXOSOME MULTIENZYME RIBONUCLEASE COMPLEX; GENOMIC INSTABILITY; HUMANS; MUTAGENESIS; TRANSCRIPTION, GENETIC;

EID: 84945438609     PISSN: 00652776     EISSN: 15578445     Source Type: Book Series    
DOI: 10.1016/bs.ai.2015.04.002     Document Type: Chapter

References (213)

1. Adelman K., Lis J.T. Promoter-proximal pausing of RNA polymerase II: Emerging roles in metazoans. Nature Reviews Genetics 2012, 13:720.
2. Adelman K., Marr M.T., Werner J., Saunders A., Ni Z., Andrulis E.D., et al. Efficient release from promoter-proximal stall sites requires transcript cleavage factor TFIIS. Molecular Cell 2005, 17:103.
3. Aguilera A., Garcia-Muse T. R loops: From transcription byproducts to threats to genome stability. Molecular Cell 2012, 46:115.
4. Aguilera A., Klein H.L. HPR1, a novel yeast gene that prevents intrachromosomal excision recombination, shows carboxy-terminal homology to the Saccharomyces cerevisiae TOP1 gene. Molecular and Cellular Biology 1990, 10:1439.
5. Allmang C., Kufel J., Chanfreau G., Mitchell P., Petfalski E., Tollervey D. Functions of the exosome in rRNA, snoRNA and snRNA synthesis. The EMBO Journal 1999, 18:5399.
6. Allmang C., Petfalski E., Podtelejnikov A., Mann M., Tollervey D., Mitchell P. The yeast exosome and human PM-Scl are related complexes of 3' -> 5' exonucleases. Genes & Development 1999, 13:2148.
7. Almada A.E., Wu X., Kriz A.J., Burge C.B., Sharp P.A. Promoter directionality is controlled by U1 snRNP and polyadenylation signals. Nature 2013, 499:360.
8. Andersen P.R., Domanski M., Kristiansen M.S., Storvall H., Ntini E., Verheggen C., et al. The human cap-binding complex is functionally connected to the nuclear RNA exosome. Nature Structural & Molecular Biology 2013, 20:1367.
9. Andrulis E.D., Werner J., Nazarian A., Erdjument-Bromage H., Tempst P., Lis J.T. The RNA processing exosome is linked to elongating RNA polymerase II in Drosophila. Nature 2002, 420:837.
10. Anindya R., Aygun O., Svejstrup J.Q. Damage-induced ubiquitylation of human RNA polymerase II by the ubiquitin ligase Nedd4, but not Cockayne syndrome proteins or BRCA1. Molecular Cell 2007, 28:386.
11. Arigo J.T., Eyler D.E., Carroll K.L., Corden J.L. Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. Molecular Cell 2006, 23:841.
12. Bachl J., Carlson C., Gray-Schopfer V., Dessing M., Olsson C. Increased transcription levels induce higher mutation rates in a hypermutating cell line. Journal of Immunology 2001, 166:5051.
13. Barski A., Cuddapah S., Cui K., Roh T.Y., Schones D.E., Wang Z., et al. High-resolution profiling of histone methylations in the human genome. Cell 2007, 129:823.
14. Basu U., Meng F.L., Keim C., Grinstein V., Pefanis E., Eccleston J., et al. The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates. Cell 2011, 144:353.
15. Bentley D.L., Groudine M. A block to elongation is largely responsible for decreased transcription of c-myc in differentiated HL60 cells. Nature 1986, 321:702.
16. Berg M.G., Singh L.N., Younis I., Liu Q., Pinto A.M., Kaida D., et al. U1 snRNP determines mRNA length and regulates isoform expression. Cell 2012, 150:53.
17. Betz A.G., Milstein C., Gonzalez-Fernandez A., Pannell R., Larson T., Neuberger M.S. Elements regulating somatic hypermutation of an immunoglobulin kappa gene: Critical role for the intron enhancer/matrix attachment region. Cell 1994, 77:239.
18. Biffi G., Tannahill D., McCafferty J., Balasubramanian S. Quantitative visualization of DNA G-quadruplex structures in human cells. Nature Chemistry 2013, 5:182.
19. Bochman M.L., Paeschke K., Zakian V.A. DNA secondary structures: Stability and function of G-quadruplex structures. Nature Reviews Genetics 2012, 13:770.
20. Boczonadi V., Muller J.S., Pyle A., Munkley J., Dor T., Quartararo J., et al. EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. Nature Communications 2014, 5:4287.
21. Bonneau F., Basquin J., Ebert J., Lorentzen E., Conti E. The yeast exosome functions as a macromolecular cage to channel RNA substrates for degradation. Cell 2009, 139:547.
22. Both G.W., Taylor L., Pollard J.W., Steele E.J. Distribution of mutations around rearranged heavy-chain antibody variable-region genes. Molecular and Cellular Biology 1990, 10:5187.
23. Boxer L.M., Dang C.V. Translocations involving c-myc and c-myc function. Oncogene 2001, 20:5595.
24. Bransteitter R., Pham P., Scharff M.D., Goodman M.F. Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Proceedings of the National Academy of Sciences of the United States of America 2003, 100:4102.
25. Carvalho S., Raposo A.C., Martins F.B., Grosso A.R., Sridhara S.C., Rino J., et al. Histone methyltransferase SETD2 coordinates FACT recruitment with nucleosome dynamics during transcription. Nucleic Acids Research 2013, 41:2881.
26. Castellano-Pozo M., Santos-Pereira J.M., Rondon A.G., Barroso S., Andujar E., Perez-Alegre M., et al. R loops are linked to histone h3 s10 phosphorylation and chromatin condensation. Molecular Cell 2013, 52:583.
27. Chan Y.A., Hieter P., Stirling P.C. Mechanisms of genome instability induced by RNA-processing defects. Trends in Genetics: TIG 2014, 30:245.
28. Chapman M.A., Lawrence M.S., Keats J.J., Cibulskis K., Sougnez C., Schinzel A.C., et al. Initial genome sequencing and analysis of multiple myeloma. Nature 2011, 471:467.
29. Chaudhuri J., Khuong C., Alt F.W. Replication protein A interacts with AID to promote deamination of somatic hypermutation targets. Nature 2004, 430:992.
30. Chaudhuri J., Tian M., Khuong C., Chua K., Pinaud E., Alt F.W. Transcription-targeted DNA deamination by the AID antibody diversification enzyme. Nature 2003, 422:726.
31. Chen Y.Z., Bennett C.L., Huynh H.M., Blair I.P., Puls I., Irobi J., et al. DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). American Journal of Human Genetics 2004, 74:1128.
32. Chiarle R., Zhang Y., Frock R.L., Lewis S.M., Molinie B., Ho Y.J., et al. Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells. Cell 2011, 147:107.
33. Chlebowski A., Lubas M., Jensen T.H., Dziembowski A. RNA decay machines: The exosome. Biochimica et Biophysica Acta 2013, 1829:552.
34. Churchman L.S., Weissman J.S. Nascent transcript sequencing visualizes transcription at nucleotide resolution. Nature 2011, 469:368.
35. Cigudosa J.C., Parsa N.Z., Louie D.C., Filippa D.A., Jhanwar S.C., Johansson B., et al. Cytogenetic analysis of 363 consecutively ascertained diffuse large B-cell lymphomas. Genes, Chromosomes & Cancer 1999, 25:123.
36. Core L.J., Waterfall J.J., Lis J.T. Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 2008, 322:1845.
37. Creamer T.J., Darby M.M., Jamonnak N., Schaughency P., Hao H., Wheelan S.J., et al. Transcriptome-wide binding sites for components of the Saccharomyces cerevisiae non-poly(A) termination pathway: Nrd1, Nab3, and Sen1. PLoS Genetics 2011, 7:e1002329.
38. Cristodero M., Bottcher B., Diepholz M., Scheffzek K., Clayton C. The Leishmania tarentolae exosome: Purification and structural analysis by electron microscopy. Molecular and Biochemical Parasitology 2008, 159:24.
39. Dalla-Favera R., Bregni M., Erikson J., Patterson D., Gallo R.C., Croce C.M. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proceedings of the National Academy of Sciences of the United States of America 1982, 79:7824.
40. Daniels G.A., Lieber M.R. RNA:DNA complex formation upon transcription of immunoglobulin switch regions: Implications for the mechanism and regulation of class switch recombination. Nucleic Acids Research 1995, 23:5006.
41. Dickerson S.K., Market E., Besmer E., Papavasiliou F.N. AID mediates hypermutation by deaminating single stranded DNA. The Journal of Experimental Medicine 2003, 197:1291.
42. Ding L., Ley T.J., Larson D.E., Miller C.A., Koboldt D.C., Welch J.S., et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 2012, 481:506.
43. Di Noia J., Neuberger M.S. Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase. Nature 2002, 419:43.
44. Doma M.K., Parker R. Endonucleolytic cleavage of eukaryotic mRNAs with stalls in translation elongation. Nature 2006, 440:561.
45. Dominguez-Sanchez M.S., Barroso S., Gomez-Gonzalez B., Luna R., Aguilera A. Genome instability and transcription elongation impairment in human cells depleted of THO/TREX. PLoS Genetics 2011, 7:e1002386.
46. Duquette M.L., Handa P., Vincent J.A., Taylor A.F., Maizels N. Intracellular transcription of G-rich DNAs induces formation of G-loops, novel structures containing G4 DNA. Genes & Development 2004, 18:1618.
47. Duquette M.L., Huber M.D., Maizels N. G-rich proto-oncogenes are targeted for genomic instability in B-cell lymphomas. Cancer Research 2007, 67:2586.
48. Dutta D., Shatalin K., Epshtein V., Gottesman M.E., Nudler E. Linking RNA polymerase backtracking to genome instability in E. coli. Cell 2011, 146:533.
49. Dziembowski A., Lorentzen E., Conti E., Seraphin B. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nature Structural & Molecular Biology 2007, 14:15.
50. Egloff S., Dienstbier M., Murphy S. Updating the RNA polymerase CTD code: Adding gene-specific layers. Trends in Genetics: TIG 2012, 28:333.
51. El Hage A., French S.L., Beyer A.L., Tollervey D. Loss of Topoisomerase I leads to R-loop-mediated transcriptional blocks during ribosomal RNA synthesis. Genes & Development 2010, 24:1546.
52. Flynn R.A., Almada A.E., Zamudio J.R., Sharp P.A. Antisense RNA polymerase II divergent transcripts are P-TEFb dependent and substrates for the RNA exosome. Proceedings of the National Academy of Sciences of the United States of America 2011, 108:10460.
53. Frey S., Bertocci B., Delbos F., Quint L., Weill J.C., Reynaud C.A. Mismatch repair deficiency interferes with the accumulation of mutations in chronically stimulated B cells and not with the hypermutation process. Immunity 1998, 9:127.
54. Frischmeyer P.A., van Hoof A., O'Donnell K., Guerrerio A.L., Parker R., Dietz H.C. An mRNA surveillance mechanism that eliminates transcripts lacking termination codons. Science 2002, 295:2258.
55. Fukita Y., Jacobs H., Rajewsky K. Somatic hypermutation in the heavy chain locus correlates with transcription. Immunity 1998, 9:105.
56. Gan W., Guan Z., Liu J., Gui T., Shen K., Manley J.L., et al. R-loop-mediated genomic instability is caused by impairment of replication fork progression. Genes & Development 2011, 25:2041.
57. Gartenberg M.R., Wang J.C. Positive supercoiling of DNA greatly diminishes mRNA synthesis in yeast. Proceedings of the National Academy of Sciences of the United States of America 1992, 89:11461.
58. Gazumyan A., Bothmer A., Klein I.A., Nussenzweig M.C., McBride K.M. Activation-induced cytidine deaminase in antibody diversification and chromosome translocation. Advances in Cancer Research 2012, 113:167.
59. Ginno P.A., Lott P.L., Christensen H.C., Korf I., Chedin F. R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters. Molecular Cell 2012, 45:814.
60. Gnatt A.L., Cramer P., Fu J., Bushnell D.A., Kornberg R.D. Structural basis of transcription: An RNA polymerase II elongation complex at 3.3 A resolution. Science 2001, 292:1876.
61. Gomez-Gonzalez B., Aguilera A. Activation-induced cytidine deaminase action is strongly stimulated by mutations of the THO complex. Proceedings of the National Academy of Sciences of the United States of America 2007, 104:8409.
62. Gordon M.S., Kanegai C.M., Doerr J.R., Wall R. Somatic hypermutation of the B cell receptor genes B29 (Igbeta, CD79b) and mb1 (Igalpha, CD79a). Proceedings of the National Academy of Sciences of the United States of America 2003, 100:4126.
63. Grzechnik P., Kufel J. Polyadenylation linked to transcription termination directs the processing of snoRNA precursors in yeast. Molecular Cell 2008, 32:247.
64. Gudipati R.K., Villa T., Boulay J., Libri D. Phosphorylation of the RNA polymerase II C-terminal domain dictates transcription termination choice. Nature Structural & Molecular Biology 2008, 15:786.
65. Gudipati R.K., Xu Z., Lebreton A., Seraphin B., Steinmetz L.M., Jacquier A., et al. Extensive degradation of RNA precursors by the exosome in wild-type cells. Molecular Cell 2012, 48:409.
66. Guenther M.G., Levine S.S., Boyer L.A., Jaenisch R., Young R.A. A chromatin landmark and transcription initiation at most promoters in human cells. Cell 2007, 130:77.
67. Guikema J.E., Linehan E.K., Tsuchimoto D., Nakabeppu Y., Strauss P.R., Stavnezer J., et al. APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination. The Journal of Experimental Medicine 2007, 204:3017.
68. Hakim O., Resch W., Yamane A., Klein I., Kieffer-Kwon K.R., Jankovic M., et al. DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes. Nature 2012, 484:69.
69. Hazelbaker D.Z., Marquardt S., Wlotzka W., Buratowski S. Kinetic competition between RNA Polymerase II and Sen1-dependent transcription termination. Molecular Cell 2013, 49:55.
70. Helmrich A., Ballarino M., Nudler E., Tora L. Transcription-replication encounters, consequences and genomic instability. Nature Structural & Molecular Biology 2013, 20:412.
71. Helmrich A., Ballarino M., Tora L. Collisions between replication and transcription complexes cause common fragile site instability at the longest human genes. Molecular Cell 2011, 44:966.
72. Henriques T., Gilchrist D.A., Nechaev S., Bern M., Muse G.W., Burkholder A., et al. Stable pausing by RNA polymerase II provides an opportunity to target and integrate regulatory signals. Molecular Cell 2013, 52:517.
73. Hirano M., Das S., Guo P., Cooper M.D. The evolution of adaptive immunity in vertebrates. Advances in Immunology 2011, 109:125.
74. Hobson D.J., Wei W., Steinmetz L.M., Svejstrup J.Q. RNA polymerase II collision interrupts convergent transcription. Molecular Cell 2012, 48:365.
75. Huertas P., Aguilera A. Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination. Molecular Cell 2003, 12:711.
76. Imai K., Slupphaug G., Lee W.I., Revy P., Nonoyama S., Catalan N., et al. Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. Nature Immunology 2003, 4:1023.
77. Januszyk K., Lima C.D. The eukaryotic RNA exosome. Current Opinion in Structural Biology 2014, 24C:132.
78. Januszyk K., Liu Q., Lima C.D. Activities of human RRP6 and structure of the human RRP6 catalytic domain. RNA 2011, 17:1566.
79. Jensen T.H., Jacquier A., Libri D. Dealing with pervasive transcription. Molecular Cell 2013, 52:473.
80. Kaida D., Berg M.G., Younis I., Kasim M., Singh L.N., Wan L., et al. U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation. Nature 2010, 468:664.
81. Keim C., Kazadi D., Rothschild G., Basu U. Regulation of AID, the B-cell genome mutator. Genes & Development 2013, 27:1.
82. Kenter A.L. AID targeting is dependent on RNA polymerase II pausing. Seminars in Immunology 2012, 24:281.
83. Khamlichi A.A., Glaudet F., Oruc Z., Denis V., Le Bert M., Cogne M. Immunoglobulin class-switch recombination in mice devoid of any S mu tandem repeat. Blood 2004, 103:3828.
84. Kim H.D., Choe J., Seo Y.S. The sen1(+) gene of Schizosaccharomyces pombe, a homologue of budding yeast SEN1, encodes an RNA and DNA helicase. Biochemistry 1999, 38:14697.
85. Kim N., Jinks-Robertson S. Transcription as a source of genome instability. Nature Reviews Genetics 2012, 13:204.
86. Kim K.Y., Levin D.E. Mpk1 MAPK association with the Paf1 complex blocks Sen1-mediated premature transcription termination. Cell 2011, 144:745.
87. Kim M., Vasiljeva L., Rando O.J., Zhelkovsky A., Moore C., Buratowski S. Distinct pathways for snoRNA and mRNA termination. Molecular Cell 2006, 24:723.
88. King I.F., Yandava C.N., Mabb A.M., Hsiao J.S., Huang H.S., Pearson B.L., et al. Topoisomerases facilitate transcription of long genes linked to autism. Nature 2013, 501:58.
89. Klein B.J., Bose D., Baker K.J., Yusoff Z.M., Zhang X., Murakami K.S. RNA polymerase and transcription elongation factor Spt4/5 complex structure. Proceedings of the National Academy of Sciences of the United States of America 2011, 108:546.
90. Klein I.A., Resch W., Jankovic M., Oliveira T., Yamane A., Nakahashi H., et al. Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell 2011, 147:95.
91. Kobayashi M., Aida M., Nagaoka H., Begum N.A., Kitawaki Y., Nakata M., et al. AID-induced decrease in topoisomerase 1 induces DNA structural alteration and DNA cleavage for class switch recombination. Proceedings of the National Academy of Sciences of the United States of America 2009, 106:22375.
92. Kodgire P., Mukkawar P., Ratnam S., Martin T.E., Storb U. Changes in RNA polymerase II progression influence somatic hypermutation of Ig-related genes by AID. The Journal of Experimental Medicine 2013, 210:1481.
93. Korzheva N., Mustaev A., Kozlov M., Malhotra A., Nikiforov V., Goldfarb A., et al. A structural model of transcription elongation. Science 2000, 289:619.
94. Kwak H., Lis J.T. Control of transcriptional elongation. Annual Review of Genetics 2013, 47:483.
95. LaCava J., Houseley J., Saveanu C., Petfalski E., Thompson E., Jacquier A., et al. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 2005, 121:713.
96. Lam E.Y., Beraldi D., Tannahill D., Balasubramanian S. G-quadruplex structures are stable and detectable in human genomic DNA. Nature Communications 2013, 4:1796.
97. Larson M.H., Mooney R.A., Peters J.M., Windgassen T., Nayak D., Gross C.A., et al. A pause sequence enriched at translation start sites drives transcription dynamics in vivo. Science 2014, 344:1042.
98. Lebecque S.G., Gearhart P.J. Boundaries of somatic mutation in rearranged immunoglobulin genes: 5' boundary is near the promoter, and 3' boundary is approximately 1kb from V(D)J gene. The Journal of Experimental Medicine 1990, 172:1717.
99. Lebreton A., Tomecki R., Dziembowski A., Seraphin B. Endonucleolytic RNA cleavage by a eukaryotic exosome. Nature 2008, 456:993.
100. Lee C.G., Kinoshita K., Arudchandran A., Cerritelli S.M., Crouch R.J., Honjo T. Quantitative regulation of class switch recombination by switch region transcription. The Journal of Experimental Medicine 2001, 194:365.
101. Lemay J.F., Larochelle M., Marguerat S., Atkinson S., Bahler J., Bachand F. The RNA exosome promotes transcription termination of backtracked RNA polymerase II. Nature Structural & Molecular Biology 2014, 21:919.
102. Lennon G.G., Perry R.P. C mu-containing transcripts initiate heterogeneously within the IgH enhancer region and contain a novel 5'-nontranslatable exon. Nature 1985, 318:475.
103. Li X., Manley J.L. Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability. Cell 2005, 122:365.
104. Li S.C., Rothman P.B., Zhang J., Chan C., Hirsh D., Alt F.W. Expression of I mu-C gamma hybrid germline transcripts subsequent to immunoglobulin heavy chain class switching. International Immunology 1994, 6:491.
105. Li G., White C.A., Lam T., Pone E.J., Tran D.C., Hayama K.L., et al. Combinatorial H3K9acS10ph histone modification in IgH locus S regions targets 14-3-3 adaptors and AID to specify antibody class-switch DNA recombination. Cell Reports 2013, 5:702.
106. Liu J.J., Bratkowski M.A., Liu X., Niu C.Y., Ke A., Wang H.W. Visualization of distinct substrate-recruitment pathways in the yeast exosome by EM. Nature Structural & Molecular Biology 2014, 21:95.
107. Liu M., Duke J.L., Richter D.J., Vinuesa C.G., Goodnow C.C., Kleinstein S.H., et al. Two levels of protection for the B cell genome during somatic hypermutation. Nature 2008, 451:841.
108. Liu Q., Greimann J.C., Lima C.D. Reconstitution, activities, and structure of the eukaryotic RNA exosome. Cell 2006, 127:1223.
109. Liu L.F., Wang J.C. Supercoiling of the DNA template during transcription. Proceedings of the National Academy of Sciences of the United States of America 1987, 84:7024.
110. Lorentzen E., Basquin J., Tomecki R., Dziembowski A., Conti E. Structure of the active subunit of the yeast exosome core, Rrp44: Diverse modes of substrate recruitment in the RNase II nuclease family. Molecular Cell 2008, 29:717.
111. Lorentzen E., Walter P., Fribourg S., Evguenieva-Hackenberg E., Klug G., Conti E. The archaeal exosome core is a hexameric ring structure with three catalytic subunits. Nature Structural & Molecular Biology 2005, 12:575.
112. Lubas M., Andersen P.R., Schein A., Dziembowski A., Kudla G., Jensen T.H. The human nuclear exosome targeting complex is loaded onto newly synthesized RNA to direct early ribonucleolysis. Cell Reports 2015, 10:178.
113. Lubas M., Christensen M.S., Kristiansen M.S., Domanski M., Falkenby L.G., Lykke-Andersen S., et al. Interaction profiling identifies the human nuclear exosome targeting complex. Molecular Cell 2011, 43:624.
114. Lykke-Andersen S., Brodersen D.E., Jensen T.H. Origins and activities of the eukaryotic exosome. Journal of Cell Science 2009, 122:1487.
115. Makino D.L., Baumgartner M., Conti E. Crystal structure of an RNA-bound 11-subunit eukaryotic exosome complex. Nature 2013, 495:70.
116. Martinez-Rucobo F.W., Sainsbury S., Cheung A.C., Cramer P. Architecture of the RNA polymerase-Spt4/5 complex and basis of universal transcription processivity. The EMBO Journal 2011, 30:1302.
117. Masani S., Han L., Yu K. Apurinic/apyrimidinic endonuclease 1 is the essential nuclease during immunoglobulin class switch recombination. Molecular and Cellular Biology 2013, 33:1468.
118. Maul R.W., Saribasak H., Martomo S.A., McClure R.L., Yang W., Vaisman A., et al. Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions. Nature Immunology 2011, 12:70.
119. Meng F.L., Du Z., Federation A., Hu J., Wang Q., Kieffer-Kwon K.R., et al. Convergent transcription at intragenic super-enhancers targets AID-initiated genomic instability. Cell 2014, 159:1538.
120. Milstein C., Neuberger M.S., Staden R. Both DNA strands of antibody genes are hypermutation targets. Proceedings of the National Academy of Sciences of the United States of America 1998, 95:8791.
121. Mischo H.E., Gomez-Gonzalez B., Grzechnik P., Rondon A.G., Wei W., Steinmetz L., et al. Yeast Sen1 helicase protects the genome from transcription-associated instability. Molecular Cell 2011, 41:21.
122. Mitchell P., Petfalski E., Shevchenko A., Mann M., Tollervey D. The exosome: A conserved eukaryotic RNA processing complex containing multiple 3'->5' exoribonucleases. Cell 1997, 91:457.
123. Mitchell P., Petfalski E., Tollervey D. The 3' end of yeast 5.8S rRNA is generated by an exonuclease processing mechanism. Genes & Development 1996, 10:502.
124. Mitchell P., Tollervey D. An NMD pathway in yeast involving accelerated deadenylation and exosome-mediated 3'->5' degradation. Molecular Cell 2003, 11:1405.
125. Moreira M.C., Klur S., Watanabe M., Nemeth A.H., Le Ber I., Moniz J.C., et al. Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nature Genetics 2004, 36:225.
126. Muramatsu M., Kinoshita K., Fagarasan S., Yamada S., Shinkai Y., Honjo T. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 2000, 102:553.
127. Muramatsu M., Sankaranand V.S., Anant S., Sugai M., Kinoshita K., Davidson N.O., et al. Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells. The Journal of Biological Chemistry 1999, 274:18470.
128. Nambu Y., Sugai M., Gonda H., Lee C.G., Katakai T., Agata Y., et al. Transcription-coupled events associating with immunoglobulin switch region chromatin. Science 2003, 302:2137.
129. Neil H., Malabat C., d'Aubenton-Carafa Y., Xu Z., Steinmetz L.M., Jacquier A. Widespread bidirectional promoters are the major source of cryptic transcripts in yeast. Nature 2009, 457:1038.
130. Ntini E., Jarvelin A.I., Bornholdt J., Chen Y., Boyd M., Jorgensen M., et al. Polyadenylation site-induced decay of upstream transcripts enforces promoter directionality. Nature Structural & Molecular Biology 2013, 20:923.
131. Nudler E., Mustaev A., Lukhtanov E., Goldfarb A. The RNA-DNA hybrid maintains the register of transcription by preventing backtracking of RNA polymerase. Cell 1997, 89:33.
132. Nussenzweig A., Nussenzweig M.C. Origin of chromosomal translocations in lymphoid cancer. Cell 2010, 141:27.
133. Pasqualucci L., Migliazza A., Fracchiolla N., William C., Neri A., Baldini L., et al. BCL-6 mutations in normal germinal center B cells: Evidence of somatic hypermutation acting outside Ig loci. Proceedings of the National Academy of Sciences of the United States of America 1998, 95:11816.
134. Pasqualucci L., Neumeister P., Goossens T., Nanjangud G., Chaganti R.S., Kuppers R., et al. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature 2001, 412:341.
135. Pavri R., Gazumyan A., Jankovic M., Di Virgilio M., Klein I., Ansarah-Sobrinho C., et al. Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5. Cell 2010, 143:122.
136. Pefanis E., Wang J., Rothschild G., Lim J., Chao J., Rabadan R., et al. Noncoding RNA transcription targets AID to divergently transcribed loci in B cells. Nature 2014, 514:389.
137. Peters A., Storb U. Somatic hypermutation of immunoglobulin genes is linked to transcription initiation. Immunity 1996, 4:57.
138. Petersen S., Casellas R., Reina-San-Martin B., Chen H.T., Difilippantonio M.J., Wilson P.C., et al. AID is required to initiate Nbs1/gamma-H2AX focus formation and mutations at sites of class switching. Nature 2001, 414:660.
139. Petersen-Mahrt S.K., Harris R.S., Neuberger M.S. AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature 2002, 418:99.
140. Piruat J.I., Aguilera A. A novel yeast gene, THO2, is involved in RNA pol II transcription and provides new evidence for transcriptional elongation-associated recombination. The EMBO Journal 1998, 17:4859.
141. Potter M., Wiener F. Plasmacytomagenesis in mice: Model of neoplastic development dependent upon chromosomal translocations. Carcinogenesis 1992, 13:1681.
142. Preker P., Nielsen J., Kammler S., Lykke-Andersen S., Christensen M.S., Mapendano C.K., et al. RNA exosome depletion reveals transcription upstream of active human promoters. Science 2008, 322:1851.
143. Qian J., Wang Q., Dose M., Pruett N., Kieffer-Kwon K.R., Resch W., et al. B cell super-enhancers and regulatory clusters recruit AID tumorigenic activity. Cell 2014, 159:1524.
144. Rada C., Di Noia J.M., Neuberger M.S. Mismatch recognition and uracil excision provide complementary paths to both Ig switching and the A/T-focused phase of somatic mutation. Molecular Cell 2004, 16:163.
145. Rada C., Ehrenstein M.R., Neuberger M.S., Milstein C. Hot spot focusing of somatic hypermutation in MSH2-deficient mice suggests two stages of mutational targeting. Immunity 1998, 9:135.
146. Rada C., Williams G.T., Nilsen H., Barnes D.E., Lindahl T., Neuberger M.S. Immunoglobulin isotype switching is inhibited and somatic hypermutation perturbed in UNG-deficient mice. Current Biology: CB 2002, 12:1748.
147. Rahl P.B., Lin C.Y., Seila A.C., Flynn R.A., McCuine S., Burge C.B., et al. c-Myc regulates transcriptional pause release. Cell 2010, 141:432.
148. Rajagopal D., Maul R.W., Ghosh A., Chakraborty T., Khamlichi A.A., Sen R., et al. Immunoglobulin switch mu sequence causes RNA polymerase II accumulation and reduces dA hypermutation. The Journal of Experimental Medicine 2009, 206:1237.
149. Ramiro A.R., Jankovic M., Callen E., Difilippantonio S., Chen H.T., McBride K.M., et al. Role of genomic instability and p53 in AID-induced c-myc-Igh translocations. Nature 2006, 440:105.
150. Ramiro A.R., Jankovic M., Eisenreich T., Difilippantonio S., Chen-Kiang S., Muramatsu M., et al. AID is required for c-myc/IgH chromosome translocations in vivo. Cell 2004, 118:431.
151. Ramiro A.R., Stavropoulos P., Jankovic M., Nussenzweig M.C. Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand. Nature Immunology 2003, 4:452.
152. Reaban M.E., Griffin J.A. Induction of RNA-stabilized DNA conformers by transcription of an immunoglobulin switch region. Nature 1990, 348:342.
153. Renner D.B., Yamaguchi Y., Wada T., Handa H., Price D.H. A highly purified RNA polymerase II elongation control system. The Journal of Biological Chemistry 2001, 276:42601.
154. Revy P., Muto T., Levy Y., Geissmann F., Plebani A., Sanal O., et al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 2000, 102:565.
155. Rhee H.S., Pugh B.F. Genome-wide structure and organization of eukaryotic pre-initiation complexes. Nature 2012, 483:295.
156. Richard P., Feng S., Manley J.L. A SUMO-dependent interaction between Senataxin and the exosome, disrupted in the neurodegenerative disease AOA2, targets the exosome to sites of transcription-induced DNA damage. Genes & Development 2013, 27:2227.
157. Robbiani D.F., Bothmer A., Callen E., Reina-San-Martin B., Dorsett Y., Difilippantonio S., et al. AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations. Cell 2008, 135:1028.
158. Robbiani D.F., Bunting S., Feldhahn N., Bothmer A., Camps J., Deroubaix S., et al. AID produces DNA double-strand breaks in non-Ig genes and mature B cell lymphomas with reciprocal chromosome translocations. Molecular Cell 2009, 36:631.
159. Roberts R.W., Crothers D.M. Stability and properties of double and triple helices: Dramatic effects of RNA or DNA backbone composition. Science 1992, 258:1463.
160. Rondon A.G., Mischo H.E., Kawauchi J., Proudfoot N.J. Fail-safe transcriptional termination for protein-coding genes in S. cerevisiae. Molecular cell 2009, 36:88.
161. Rouaud P., Saintamand A., Saad F., Carrion C., Lecardeur S., Cogne M., et al. Elucidation of the enigmatic IgD class-switch recombination via germline deletion of the IgH 3' regulatory region. The Journal of Experimental Medicine 2014, 211:975.
162. Roy D., Zhang Z., Lu Z., Hsieh C.L., Lieber M.R. Competition between the RNA transcript and the nontemplate DNA strand during R-loop formation in vitro: A nick can serve as a strong R-loop initiation site. Molecular and Cellular Biology 2010, 30:146.
163. Ruiz J.F., Gomez-Gonzalez B., Aguilera A. AID induces double-strand breaks at immunoglobulin switch regions and c-MYC causing chromosomal translocations in yeast THO mutants. PLoS Genetics 2011, 7:e1002009.
164. Schaeffer D., Clark A., Klauer A.A., Tsanova B., van Hoof A. Functions of the cytoplasmic exosome. Advances in Experimental Medicine and Biology 2010, 702:79.
165. Schaeffer D., Tsanova B., Barbas A., Reis F.P., Dastidar E.G., Sanchez-Rotunno M., et al. The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities. Nature Structural & Molecular Biology 2009, 16:56.
166. Schulz D., Schwalb B., Kiesel A., Baejen C., Torkler P., Gagneur J., et al. Transcriptome surveillance by selective termination of noncoding RNA synthesis. Cell 2013, 155:1075.
167. Seila A.C., Calabrese J.M., Levine S.S., Yeo G.W., Rahl P.B., Flynn R.A., et al. Divergent transcription from active promoters. Science 2008, 322:1849.
168. Shen H.M., Peters A., Baron B., Zhu X., Storb U. Mutation of BCL-6 gene in normal B cells by the process of somatic hypermutation of Ig genes. Science 1998, 280:1750.
169. Shimizu A., Takahashi N., Yaoita Y., Honjo T. Organization of the constant-region gene family of the mouse immunoglobulin heavy chain. Cell 1982, 28:499.
170. Shinkura R., Tian M., Smith M., Chua K., Fujiwara Y., Alt F.W. The influence of transcriptional orientation on endogenous switch region function. Nature Immunology 2003, 4:435.
171. Skourti-Stathaki K., Proudfoot N.J. A double-edged sword: R loops as threats to genome integrity and powerful regulators of gene expression. Genes & Development 2014, 28:1384.
172. Skourti-Stathaki K., Proudfoot N.J., Gromak N. Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination. Molecular Cell 2011, 42:794.
173. Staals R.H., Bronkhorst A.W., Schilders G., Slomovic S., Schuster G., Heck A.J., et al. Dis3-like 1: A novel exoribonuclease associated with the human exosome. The EMBO Journal 2010, 29:2358.
174. Staszewski O., Baker R.E., Ucher A.J., Martier R., Stavnezer J., Guikema J.E. Activation-induced cytidine deaminase induces reproducible DNA breaks at many non-Ig Loci in activated B cells. Molecular Cell 2011, 41:232.
175. Stavnezer-Nordgren J., Sirlin S. Specificity of immunoglobulin heavy chain switch correlates with activity of germline heavy chain genes prior to switching. The EMBO Journal 1986, 5:95.
176. Steinmetz E.J., Conrad N.K., Brow D.A., Corden J.L. RNA-binding protein Nrd1 directs poly(A)-independent 3'-end formation of RNA polymerase II transcripts. Nature 2001, 413:327.
177. Storb U. Why does somatic hypermutation by AID require transcription of its target genes?. Advances in Immunology 2014, 122:253.
178. Sun J., Keim C.D., Wang J., Kazadi D., Oliver P.M., Rabadan R., et al. E3-ubiquitin ligase Nedd4 determines the fate of AID-associated RNA polymerase II in B cells. Genes & Development 2013, 27:1821.
179. Sun J., Rothschild G., Pefanis E., Basu U. Transcriptional stalling in B-lymphocytes: A mechanism for antibody diversification and maintenance of genomic integrity. Transcription 2013, 4:127.
180. Takahashi S., Araki Y., Sakuno T., Katada T. Interaction between Ski7p and Upf1p is required for nonsense-mediated 3'-to-5' mRNA decay in yeast. The EMBO Journal 2003, 22:3951.
181. Taub R., Kirsch I., Morton C., Lenoir G., Swan D., Tronick S., et al. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proceedings of the National Academy of Sciences of the United States of America 1982, 79:7837.
182. Thiebaut M., Kisseleva-Romanova E., Rougemaille M., Boulay J., Libri D. Transcription termination and nuclear degradation of cryptic unstable transcripts: A role for the nrd1-nab3 pathway in genome surveillance. Molecular Cell 2006, 23:853.
183. Tomecki R., Kristiansen M.S., Lykke-Andersen S., Chlebowski A., Larsen K.M., Szczesny R.J., et al. The human core exosome interacts with differentially localized processive RNases: hDIS3 and hDIS3L. The EMBO Journal 2010, 29:2342.
184. Torchet C., Bousquet-Antonelli C., Milligan L., Thompson E., Kufel J., Tollervey D. Processing of 3'-extended read-through transcripts by the exosome can generate functional mRNAs. Molecular Cell 2002, 9:1285.
185. Tuduri S., Crabbe L., Conti C., Tourriere H., Holtgreve-Grez H., Jauch A., et al. Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription. Nature Cell Biology 2009, 11:1315.
186. Tumas-Brundage K., Manser T. The transcriptional promoter regulates hypermutation of the antibody heavy chain locus. The Journal of Experimental Medicine 1997, 185:239.
187. van Hoof A., Frischmeyer P.A., Dietz H.C., Parker R. Exosome-mediated recognition and degradation of mRNAs lacking a termination codon. Science 2002, 295:2262.
188. van Hoof A., Lennertz P., Parker R. Yeast exosome mutants accumulate 3'-extended polyadenylated forms of U4 small nuclear RNA and small nucleolar RNAs. Molecular and Cellular Biology 2000, 20:441.
189. Vasiljeva L., Buratowski S. Nrd1 interacts with the nuclear exosome for 3' processing of RNA polymerase II transcripts. Molecular Cell 2006, 21:239.
190. Vasiljeva L., Kim M., Mutschler H., Buratowski S., Meinhart A. The Nrd1-Nab3-Sen1 termination complex interacts with the Ser5-phosphorylated RNA polymerase II C-terminal domain. Nature Structural & Molecular Biology 2008, 15:795.
191. Vvedenskaya I.O., Vahedian-Movahed H., Bird J.G., Knoblauch J.G., Goldman S.R., Zhang Y., et al. Transcription. Interactions between RNA polymerase and the "core recognition element" counteract pausing. Science 2014, 344:1285.
192. Wada T., Takagi T., Yamaguchi Y., Ferdous A., Imai T., Hirose S., et al. DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs. Genes & Development 1998, 12:343.
193. Wahba L., Amon J.D., Koshland D., Vuica-Ross M. RNase H and multiple RNA biogenesis factors cooperate to prevent RNA:DNA hybrids from generating genome instability. Molecular Cell 2011, 44:978.
194. Wan J., Yourshaw M., Mamsa H., Rudnik-Schoneborn S., Menezes M.P., Hong J.E., et al. Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration. Nature Genetics 2012, 44:704.
195. Wang X., Fan M., Kalis S., Wei L., Scharff M.D. A source of the single-stranded DNA substrate for activation-induced deaminase during somatic hypermutation. Nature Communications 2014, 5:4137.
196. Wang D., Landick R. Nuclease cleavage of the upstream half of the nontemplate strand DNA in an Escherichia coli transcription elongation complex causes upstream translocation and transcriptional arrest. The Journal of Biological Chemistry 1997, 272:5989.
197. Wang Q., Oliveira T., Jankovic M., Silva I.T., Hakim O., Yao K., et al. Epigenetic targeting of activation-induced cytidine deaminase. Proceedings of the National Academy of Sciences of the United States of America 2014, 111:18667.
198. Wang L., Wuerffel R., Feldman S., Khamlichi A.A., Kenter A.L. S region sequence, RNA polymerase II, and histone modifications create chromatin accessibility during class switch recombination. The Journal of Experimental Medicine 2009, 206:1817.
199. Wasmuth E.V., Januszyk K., Lima C.D. Structure of an Rrp6-RNA exosome complex bound to poly(A) RNA. Nature 2014, 511:435.
200. Wasmuth E.V., Lima C.D. Exo- and endoribonucleolytic activities of yeast cytoplasmic and nuclear RNA exosomes are dependent on the noncatalytic core and central channel. Molecular Cell 2012, 48:133.
201. Wellinger R.E., Prado F., Aguilera A. Replication fork progression is impaired by transcription in hyperrecombinant yeast cells lacking a functional THO complex. Molecular and Cellular Biology 2006, 26:3327.
202. Westover K.D., Bushnell D.A., Kornberg R.D. Structural basis of transcription: Separation of RNA from DNA by RNA polymerase II. Science 2004, 303:1014.
203. Wlotzka W., Kudla G., Granneman S., Tollervey D. The nuclear RNA polymerase II surveillance system targets polymerase III transcripts. The EMBO Journal 2011, 30:1790.
204. Wongsurawat T., Jenjaroenpun P., Kwoh C.K., Kuznetsov V. Quantitative model of R-loop forming structures reveals a novel level of RNA-DNA interactome complexity. Nucleic Acids Research 2012, 40:e16.
205. Wyers F., Rougemaille M., Badis G., Rousselle J.C., Dufour M.E., Boulay J., et al. Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 2005, 121:725.
206. Xu Z., Wei W., Gagneur J., Perocchi F., Clauder-Munster S., Camblong J., et al. Bidirectional promoters generate pervasive transcription in yeast. Nature 2009, 457:1033.
207. Xue K., Rada C., Neuberger M.S. The in vivo pattern of AID targeting to immunoglobulin switch regions deduced from mutation spectra in msh2-/- ung-/- mice. The Journal of Experimental Medicine 2006, 203:2085.
208. Yamaguchi Y., Takagi T., Wada T., Yano K., Furuya A., Sugimoto S., et al. NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation. Cell 1999, 97:41.
209. Yamane A., Resch W., Kuo N., Kuchen S., Li Z., Sun H.W., et al. Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes. Nature Immunology 2011, 12:62.
210. Yancopoulos G.D., DePinho R.A., Zimmerman K.A., Lutzker S.G., Rosenberg N., Alt F.W. Secondary genomic rearrangement events in pre-B cells: VHDJH replacement by a LINE-1 sequence and directed class switching. The EMBO Journal 1986, 5:3259.
211. Yu K., Chedin F., Hsieh C.L., Wilson T.E., Lieber M.R. R-loops at immunoglobulin class switch regions in the chromosomes of stimulated B cells. Nature Immunology 2003, 4:442.
212. Zhang Y., Feng Y., Chatterjee S., Tuske S., Ho M.X., Arnold E., et al. Structural basis of transcription initiation. Science 2012, 338:1076.
213. Zhou Q., Li T., Price D.H. RNA polymerase II elongation control. Annual Review of Biochemistry 2012, 81:119.