Transcription Dynamics Prevent RNA-Mediated Genomic Instability through SRPK2-Dependent DDX23 Phosphorylation

Cell Reports

Volumn 18, Issue 2, 2017, Pages 334-343

  Sridhara, Sreerama Chaitanya ^a   Carvalho, Sílvia ^a   Grosso, Ana Rita ^a   Gallego Paez, Lina Marcela ^a   Carmo Fonseca, Maria ^a   de Almeida, Sérgio Fernandes ^a  

^a INSTITUTO DE MEDICINA MOLECULAR   (Portugal)

Author keywords

DDX23; genomic instability; R loops; RNA polymerase II; SRPK2; transcription dynamics

Indexed keywords

DEAD BOX PROTEIN; DEAD BOX PROTEIN 23; PROTEIN KINASE; RNA HELICASE; RNA POLYMERASE II; SERINE ARGININE PROTEIN KINASE 1; SERINE ARGININE PROTEIN KINASE 2; UNCLASSIFIED DRUG; DDX23 PROTEIN, HUMAN; PROTEIN SERINE THREONINE KINASE; SMALL NUCLEAR RIBONUCLEOPROTEIN; SRPK2 PROTEIN, HUMAN;

ADENOID CYSTIC CARCINOMA; ARTICLE; CELL NUCLEUS; CONTROLLED STUDY; CYTOPLASM; DOUBLE STRANDED DNA BREAK; GENE LOCUS; GENOMIC INSTABILITY; HUMAN; HUMAN CELL; MOLECULAR BIOLOGY; MUTATION; NUCLEIC ACID STRUCTURE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; R LOOP; RNA INTERFERENCE; RNA TRANSCRIPTION; CONFORMATION; DNA DAMAGE; GENETIC TRANSCRIPTION; GENETICS; METABOLISM; PATHOLOGY; PHOSPHORYLATION; RNA STABILITY; SPLICEOSOME; TUMOR CELL LINE;

CARCINOMA, ADENOID CYSTIC; CELL LINE, TUMOR; DEAD-BOX RNA HELICASES; DNA DAMAGE; GENOMIC INSTABILITY; HUMANS; NUCLEIC ACID CONFORMATION; PHOSPHORYLATION; PROTEIN-SERINE-THREONINE KINASES; RIBONUCLEOPROTEIN, U5 SMALL NUCLEAR; RNA INTERFERENCE; RNA POLYMERASE II; RNA STABILITY; SPLICEOSOMES; TRANSCRIPTION, GENETIC;

EID: 85009231218     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2016.12.050     Document Type: Article

References (44)

1. Achsel, T., Ahrens, K., Brahms, H., Teigelkamp, S., Lührmann, R., The human U5-220kD protein (hPrp8) forms a stable RNA-free complex with several U5-specific proteins, including an RNA unwindase, a homologue of ribosomal elongation factor EF-2, and a novel WD-40 protein. Mol. Cell. Biol. 18 (1998), 6756–6766.
2. Adelstein, D.J., Koyfman, S.A., El-Naggar, A.K., Hanna, E.Y., Biology and management of salivary gland cancers. Semin. Radiat. Oncol. 22 (2012), 245–253.
3. Agafonov, D.E., Kastner, B., Dybkov, O., Hofele, R.V., Liu, W.T., Urlaub, H., Lührmann, R., Stark, H., Molecular architecture of the human U4/U6.U5 tri-snRNP. Science 351 (2016), 1416–1420.
4. Alexander, R.D., Innocente, S.A., Barrass, J.D., Beggs, J.D., Splicing-dependent RNA polymerase pausing in yeast. Mol. Cell 40 (2010), 582–593.
5. Bhatia, V., Barroso, S.I., García-Rubio, M.L., Tumini, E., Herrera-Moyano, E., Aguilera, A., BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor PCID2. Nature 511 (2014), 362–365.
6. Boguslawski, S.J., Smith, D.E., Michalak, M.A., Mickelson, K.E., Yehle, C.O., Patterson, W.L., Carrico, R.J., Characterization of monoclonal antibody to DNA.RNA and its application to immunodetection of hybrids. J. Immunol. Methods 89 (1986), 123–130.
7. Brown, T.A., Tkachuk, A.N., Clayton, D.A., Native R-loops persist throughout the mouse mitochondrial DNA genome. J. Biol. Chem. 283 (2008), 36743–36751.
8. Buratowski, S., Progression through the RNA polymerase II CTD cycle. Mol. Cell 36 (2009), 541–546.
9. Cazalla, D., Zhu, J., Manche, L., Huber, E., Krainer, A.R., Cáceres, J.F., Nuclear export and retention signals in the RS domain of SR proteins. Mol. Cell. Biol. 22 (2002), 6871–6882.
10. Cerami, E., Gao, J., Dogrusoz, U., Gross, B.E., Sumer, S.O., Aksoy, B.A., Jacobsen, A., Byrne, C.J., Heuer, M.L., Larsson, E., et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2 (2012), 401–404.
11. Chae, Y.K., Chung, S.Y., Davis, A.A., Carneiro, B.A., Chandra, S., Kaplan, J., Kalyan, A., Giles, F.J., Adenoid cystic carcinoma: current therapy and potential therapeutic advances based on genomic profiling. Oncotarget 6 (2015), 37117–37134.
12. Domínguez-Sánchez, M.S., Barroso, S., Gómez-González, B., Luna, R., Aguilera, A., Genome instability and transcription elongation impairment in human cells depleted of THO/TREX. PLoS Genet., 7, 2011, e1002386.
13. Gao, J., Aksoy, B.A., Dogrusoz, U., Dresdner, G., Gross, B., Sumer, S.O., Sun, Y., Jacobsen, A., Sinha, R., Larsson, E., et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal., 6, 2013, pl1.
14. Ginno, P.A., Lott, P.L., Christensen, H.C., Korf, I., Chédin, F., R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters. Mol. Cell 45 (2012), 814–825.
15. Ginno, P.A., Lim, Y.W., Lott, P.L., Korf, I., Chédin, F., GC skew at the 5′ and 3′ ends of human genes links R-loop formation to epigenetic regulation and transcription termination. Genome Res. 23 (2013), 1590–1600.
16. Grainger, R.J., Beggs, J.D., Prp8 protein: at the heart of the spliceosome. RNA 11 (2005), 533–557.
17. Hamperl, S., Cimprich, K.A., The contribution of co-transcriptional RNA:DNA hybrid structures to DNA damage and genome instability. DNA Repair (Amst.) 19 (2014), 84–94.
18. Harlen, K.M., Trotta, K.L., Smith, E.E., Mosaheb, M.M., Fuchs, S.M., Churchman, L.S., Comprehensive RNA polymerase II interactomes reveal distinct and varied roles for each phospho-CTD residue. Cell Rep. 15 (2016), 2147–2158.
19. Hatchi, E., Skourti-Stathaki, K., Ventz, S., Pinello, L., Yen, A., Kamieniarz-Gdula, K., Dimitrov, S., Pathania, S., McKinney, K.M., Eaton, M.L., et al. BRCA1 recruitment to transcriptional pause sites is required for R-loop-driven DNA damage repair. Mol. Cell 57 (2015), 636–647.
20. Heidemann, M., Hintermair, C., Voß, K., Eick, D., Dynamic phosphorylation patterns of RNA polymerase II CTD during transcription. Biochim. Biophys. Acta 1829 (2013), 55–62.
21. Henriques, T., Gilchrist, D.A., Nechaev, S., Bern, M., Muse, G.W., Burkholder, A., Fargo, D.C., Adelman, K., Stable pausing by RNA polymerase II provides an opportunity to target and integrate regulatory signals. Mol. Cell 52 (2013), 517–528.
22. Ho, A.S., Kannan, K., Roy, D.M., Morris, L.G., Ganly, I., Katabi, N., Ramaswami, D., Walsh, L.A., Eng, S., Huse, J.T., et al. The mutational landscape of adenoid cystic carcinoma. Nat. Genet. 45 (2013), 791–798.
23. Huertas, P., Aguilera, A., Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination. Mol. Cell 12 (2003), 711–721.
24. Laggerbauer, B., Achsel, T., Lührmann, R., The human U5-200kD DEXH-box protein unwinds U4/U6 RNA duplices in vitro. Proc. Natl. Acad. Sci. USA 95 (1998), 4188–4192.
25. Li, X., Manley, J.L., Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability. Cell 122 (2005), 365–378.
26. Makarov, E.M., Makarova, O.V., Achsel, T., Lührmann, R., The human homologue of the yeast splicing factor prp6p contains multiple TPR elements and is stably associated with the U5 snRNP via protein-protein interactions. J. Mol. Biol. 298 (2000), 567–575.
27. Mathew, R., Hartmuth, K., Möhlmann, S., Urlaub, H., Ficner, R., Lührmann, R., Phosphorylation of human PRP28 by SRPK2 is required for integration of the U4/U6-U5 tri-snRNP into the spliceosome. Nat. Struct. Mol. Biol. 15 (2008), 435–443.
28. Mischo, H.E., Gómez-González, B., Grzechnik, P., Rondón, A.G., Wei, W., Steinmetz, L., Aguilera, A., Proudfoot, N.J., Yeast Sen1 helicase protects the genome from transcription-associated instability. Mol. Cell 41 (2011), 21–32.
29. Nojima, T., Gomes, T., Grosso, A.R., Kimura, H., Dye, M.J., Dhir, S., Carmo-Fonseca, M., Proudfoot, N.J., Mammalian NET-seq reveals genome-wide nascent transcription coupled to RNA processing. Cell 161 (2015), 526–540.
30. Phuchareon, J., Ohta, Y., Woo, J.M., Eisele, D.W., Tetsu, O., Genetic profiling reveals cross-contamination and misidentification of 6 adenoid cystic carcinoma cell lines: ACC2, ACC3, ACCM, ACCNS, ACCS and CAC2. PLoS ONE, 4, 2009, e6040.
31. Ritchie, D.B., Schellenberg, M.J., Gesner, E.M., Raithatha, S.A., Stuart, D.T., Macmillan, A.M., Structural elucidation of a PRP8 core domain from the heart of the spliceosome. Nat. Struct. Mol. Biol. 15 (2008), 1199–1205.
32. Santos-Pereira, J.M., Aguilera, A., R loops: new modulators of genome dynamics and function. Nat. Rev. Genet. 16 (2015), 583–597.
33. Santos-Pereira, J.M., García-Rubio, M.L., González-Aguilera, C., Luna, R., Aguilera, A., A genome-wide function of THSC/TREX-2 at active genes prevents transcription-replication collisions. Nucleic Acids Res. 42 (2014), 12000–12014.
34. Skourti-Stathaki, K., Proudfoot, N.J., A double-edged sword: R loops as threats to genome integrity and powerful regulators of gene expression. Genes Dev. 28 (2014), 1384–1396.
35. Skourti-Stathaki, K., Proudfoot, N.J., Gromak, N., Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination. Mol. Cell 42 (2011), 794–805.
36. Skourti-Stathaki, K., Kamieniarz-Gdula, K., Proudfoot, N.J., R-loops induce repressive chromatin marks over mammalian gene terminators. Nature 516 (2014), 436–439.
37. Sollier, J., Cimprich, K.A., Breaking bad: R-loops and genome integrity. Trends Cell Biol. 25 (2015), 514–522.
38. Teigelkamp, S., Mundt, C., Achsel, T., Will, C.L., Lührmann, R., The human U5 snRNP-specific 100-kD protein is an RS domain-containing, putative RNA helicase with significant homology to the yeast splicing factor Prp28p. RNA 3 (1997), 1313–1326.
39. Tous, C., Aguilera, A., Impairment of transcription elongation by R-loops in vitro. Biochem. Biophys. Res. Commun. 360 (2007), 428–432.
40. Tresini, M., Warmerdam, D.O., Kolovos, P., Snijder, L., Vrouwe, M.G., Demmers, J.A., van IJcken, W.F., Grosveld, F.G., Medema, R.H., Hoeijmakers, J.H., et al. The core spliceosome as target and effector of non-canonical ATM signalling. Nature 523 (2015), 53–58.
41. Varjosalo, M., Keskitalo, S., Van Drogen, A., Nurkkala, H., Vichalkovski, A., Aebersold, R., Gstaiger, M., The protein interaction landscape of the human CMGC kinase group. Cell Rep. 3 (2013), 1306–1320.
42. Wahl, M.C., Will, C.L., Lührmann, R., The spliceosome: design principles of a dynamic RNP machine. Cell 136 (2009), 701–718.
43. Zhao, D.Y., Gish, G., Braunschweig, U., Li, Y., Ni, Z., Schmitges, F.W., Zhong, G., Liu, K., Li, W., Moffat, J., et al. SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination. Nature 529 (2016), 48–53.
44. Zhou, Z., Fu, X.D., Regulation of splicing by SR proteins and SR protein-specific kinases. Chromosoma 122 (2013), 191–207.