Pyrvinium pamoate changes alternative splicing of the serotonin receptor 2C by influencing its RNA structure

Nucleic Acids Research

Volumn 41, Issue 6, 2013, Pages 3819-3832

  Shen, Manli ^a   Bellaousov, Stanislav ^e   Hiller, Michael ^b,c   De La Grange, Pierre ^d   Creamer, Trevor P ^a,h   Malina, Orit ^g   Sperling, Ruth ^g   Mathews, David H ^e   Stoilov, Peter ^f   Stamm, Stefan ^a  

^a UNIVERSITY OF KENTUCKY   (United States)

^b MAX PLANCK INSTITUTE OF MOLECULAR CELL BIOLOGY AND GENETICS   (Germany)

^c MAX PLANCK INSTITUT FÜR PHYSIK KOMPLEXER SYSTEME   (Germany)

^d SAINT LOUIS HOSPITAL   (France)

^e UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^f WEST VIRGINIA UNIVERSITY   (United States)

^g HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^h UNIVERSITY OF KENTUCKY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA PRECURSOR; PYRVINIUM EMBONATE; RNA; SEROTONIN 2C RECEPTOR;

ALTERNATIVE RNA SPLICING; ARTICLE; BASE PAIRING; CELL STRAIN HEK293; CIRCULAR DICHROISM; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DRUG MECHANISM; DRUG STRUCTURE; GENETIC ANALYSIS; GENETIC REGULATION; GENOME ANALYSIS; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; PRIORITY JOURNAL; RIBOSWITCH; RNA BINDING; RNA EDITING; RNA SECONDARY STRUCTURE; RNA SPLICING; RNA STABILITY; RNA STRUCTURE; SELECTIVE 20' HYDROXYL ACYLATION ANALYZED BY PRIMER EXTENSION ASSAY;

ALTERNATIVE SPLICING; BASE SEQUENCE; EXONS; HEK293 CELLS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MOLECULAR SEQUENCE DATA; NUCLEIC ACID CONFORMATION; PHYLOGENY; PYRVINIUM COMPOUNDS; RECEPTOR, SEROTONIN, 5-HT2C; RIBONUCLEOPROTEIN, U1 SMALL NUCLEAR; RNA EDITING; RNA PRECURSORS; RNA, DOUBLE-STRANDED; RNA, MESSENGER; SPLICEOSOMES;

EID: 84876048680     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkt063     Document Type: Article

References (50)

1. Miller, K.J. (2005) Serotonin 5-ht2c receptor agonists: potential for the treatment of obesity. Mol. Interv., 5, 282-291.
2. Flomen, R., Knight, J., Sham, P., Kerwin,R. and Makoff, A. (2004) Evidence that RNA editing modulates splice site selection in the 5-HT2C receptor gene. Nucleic Acids Res., 32, 2113-2122.
3. Kishore, S., Khanna, A., Zhang, Z., Hui, J., Balwierz, P.J., Stefan, M., Beach, C., Nicholls, R.D., Zavolan,M. and Stamm, S. (2010) The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing. Hum. Mol. Genet., 19, 1153-1164.
4. Kishore,S. and Stamm, S. (2006) The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C. Science, 311, 230-232.
5. Burns, C.M., Chu, H., Rueter, S.M., Hutchinson, L.K., Canton, H., Sanders-Bush,E. and Emeson, R.B. (1997) Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature, 387, 303-308.
6. Tecott, L.H., Sun, L.M., Akana, S.F., Strack, A.M., Lowenstein, D.H., Dallman, M.F. and Julius, D. (1995) Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature, 374, 542-546.
7. Nonogaki, K., Strack, A.M., Dallman, M.F. and Tecott, L.H. (1998) Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat. Med., 4, 1152-1156.
8. Kawahara, Y., Grimberg, A., Teegarden, S., Mombereau, C., Liu, S., Bale, T.L., Blendy, J.A. and Nishikura, K. (2008) Dysregulated editing of serotonin 2C receptor mRNAs results in energy dissipation and loss of fat mass. J. Neurosci., 28, 12834-12844.
9. Morabito, M.V., Abbas, A.I., Hood, J.L., Kesterson, R.A., Jacobs, M.M., Kump, D.S., Hachey, D.L., Roth, B.L. and Emeson, R.B. (2010) Mice with altered serotonin 2C receptor RNA editing display characteristics of Prader-Willi Syndrome. Neurobiol. Dis., 39, 169-180.
10. Sahoo, T., del Gaudio, D., German, J.R., Shinawi, M., Peters, S.U., Person, R.E., Garnica, A., Cheung, S.W. and Beaudet, A.L. (2008) Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster. Nat. Genet., 40, 719-721.
11. Duker, A.L., Ballif, B.C., Bawle, E.V., Person, R.E., Mahadevan, S., Alliman, S., Thompson, R., Traylor, R., Bejjani, B.A., Shaffer, L.G. et al. (2010) Paternally inherited microdeletion at 15q11.2 confirms a significant role for the SNORD116 C/D box snoRNA cluster in Prader-Willi syndrome. Eur. J. Hum. Genet., 18, 1196-1201.
12. Soeno, Y., Taya, Y., Stasyk, T., Huber, L.A., Aoba,T. and Huttenhofer, A. (2010) Identification of novel ribonucleo-protein complexes from the brain-specific snoRNA MBII-52. RNA, 16, 1293-3000.
13. Shen, M., Eyras, E., Wu, J., Khanna, A., Josiah, S., Rederstorff, M., Zhang, M.Q. and Stamm, S. (2011) Direct cloning of double-stranded RNAs from RNase protection analysis reveals processing patterns of C/D box snoRNAs and provides evidence for widespread antisense transcript expression. Nucleic Acids Res., 39, 9720-9730.
14. Kishore,S. and Stamm, S. (2006) Regulation of alternative splicing by snoRNAs. Cold Spring Harb. Symp. Quant. Biol., 71, 329-334.
15. Xavier, K.A., Eder, P.S. and Giordano, T. (2000) RNA as a drug target: methods for biophysical characterization and screening. Trends Biotechnol., 18, 349-356.
16. Thanaraj, T.A., Cochet,O. and Stamm, S. (2003) Misregulation of alternative splicing as a novel target for drug intervention. Pharm. Visions, 2, 4-6.
17. Schroeder, R., Waldsich,C. and Wank, H. (2000) Modulation of RNA function by aminoglycoside antibiotics. EMBO J., 19, 1-9.
18. Xu, M., Wells, K.S. and Emeson, R.B. (2006) Substrate-dependent contribution of double-stranded RNA-binding motifs to ADAR2 function. Mol. Biol. Cell, 17, 3211-3220.
19. Buratti,E. and Baralle, F.E. (2004) Influence of RNA secondary structure on the pre-mRNA splicing process. Mol. Cell. Biol., 24, 10505-10514.
20. Hiller, M., Zhang, Z., Backofen,R. and Stamm, S. (2007) pre-mRNA secondary structure and splice site selection. PLoS Genet., 3, 2147-2155.
21. Novoyatleva, T., Heinrich, B., Tang, Y., Benderska, N., Butchbach, M.E., Lorson, C.L., Lorson, M.A., Ben-Dov, C., Fehlbaum, P., Bracco, L. et al. (2008) Protein phosphatase 1 binds to the RNA recognition motif of several splicing factors and regulates alternative pre-mRNA processing. Hum. Mol. Genet., 52-70.
22. Anderson, E.S., Lin, C.H., Xiao, X., Stoilov, P., Burge, C.B. and Black, D.L. (2012) The cardiotonic steroid digitoxin regulates alternative splicing through depletion of the splicing factors SRSF3 and TRA2B. RNA, 18, 1041-1049.
23. Sumanasekera, C., Watt, D.S. and Stamm, S. (2008) Substances that can change alternative splice-site selection. Biochem. Soc. Trans., 36, 483-490.
24. Cheah, M.T., Wachter, A., Sudarsan,N. and Breaker, R.R. (2007) Control of alternative RNA splicing and gene expression by eukaryotic riboswitches. Nature, 447, 497-500.
25. Stoilov, P., Lin, C.H., Damoiseaux, R., Nikolic,J. and Black, D.L. (2008) A high-throughput screening strategy identifies cardiotonic steroids as alternative splicing modulators. Proc. Natl Acad. Sci. USA, 105, 11218-11223.
26. Stoilov, P. (2012) Screening for Alternative Splicing Modulators. In: Stamm, S., Smith,C. and Luhrmann, R. (eds), Alternative pre-mRNA splicing: Theory and Protocols. Wiley-Blackwell, Weinheim, pp. 497-508.
27. Kapur, K., Jiang, H., Xing,Y. and Wong, W.H. (2008) Cross-hybridization modeling on Affymetrix exon arrays. Bioinformatics, 24, 2887-2893.
28. Shen, S., Warzecha, C.C., Carstens, R.P. and Xing, Y. (2010) MADS+: discovery of differential splicing events from Affymetrix exon junction array data. Bioinformatics, 26, 268-269.
29. Wilkinson, K.A., Merino, E.J. and Weeks, K.M. (2006) Selective 20-hydroxyl acylation analyzed by primer extension (SHAPE): quantitative RNA structure analysis at single nucleotide resolution. Nat. Protoc., 1, 1610-1616.
30. Deigan, K.E., Li, T.W., Mathews, D.H. and Weeks, K.M. (2009) Accurate SHAPE-directed RNA structure determination. Proc. Natl Acad. Sci. USA, 106, 97-102.
31. Azubel, M., Habib, N., Sperling,R. and Sperling, J. (2006) Native spliceosomes assemble with pre-mRNA to form supraspliceosomes. J. Mol. Biol., 356, 955-966.
32. Heinrich, B., Zhang, Z., Raitskin, O., Hiller, M., Benderska, N., Hartmann, A.M., Bracco, L., Elliott, D., Ben-Ari, S., Soreq, H. et al. (2009) Heterogeneous nuclear ribonucleoprotein G regulates splice site selection by binding to CC(A/C)-rich regions in pre-mRNA. J. Biol. Chem., 284, 14303-14315.
33. Cleveland, W.S. and Devlin, S.J. (1988) Locally weighted regression: an approach to regression analysis by local fitting. J. Am. Stat. Assoc., 83, 596-610.
34. Zhang, J.H., Chung, T.D. and Oldenburg, K.R. (1999) A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J. Biomol. Screen., 4, 67-73.
35. Dickie, P., Morgan, A.R., Scraba, D.G. and von Borstel, R.C. (1986) The binding of the anthelmintic pyrvinium cation to deoxyribonucleic acid in vitro. Mol. Pharmacol., 29, 427-435.
36. Stockert, J.C., Trigoso, C.I., Llorente, A.R. and Del Castillo, P. (1991) DNA fluorescence induced by polymethine cation pyrvinium binding. Histochem. J., 23, 548-552.
37. Saraswati, S., Alfaro, M.P., Thorne, C.A., Atkinson, J., Lee,E. and Young, P.P. (2010) Pyrvinium, a potent small molecule Wnt inhibitor, promotes wound repair and post-MI cardiac remodeling. PloS One, 5, e15521.
38. Frederick, C.A., Williams, L.D., Ughetto, G., van der Marel, G.A., van Boom, J.H., Rich,A. and Wang, A.H. (1990) Structural comparison of anticancer drug-DNA complexes: adriamycin and daunomycin. Biochemistry, 29, 2538-2549.
39. Niswender, C.M., Copeland, S.C., Herrick-Davis, K., Emeson, R.B. and Sanders-Bush, E. (1999) RNA editing of the human serotonin 5-hydroxytryptamine 2C receptor silences constitutive activity. J. Biol. Chem., 274, 9472-9478.
40. Sperling, J., Azubel,M. and Sperling, R. (2008) Structure and function of the Pre-mRNA splicing machine. Structure, 16, 1605-1615.
41. Sebbag-Sznajder, N., Raitskin, O., Angenitzki, M., Sato, T.A., Sperling,J. and Sperling, R. (2012) Regulation of alternative splicing within the supraspliceosome. J. Struct. Biol., 177, 152-159.
42. Raitskin, O., Cho, D.S., Sperling, J., Nishikura,K. and Sperling, R. (2001) RNA editing activity is associated with splicing factors in lnRNP particles: the nuclear pre-mRNA processing machinery. Proc. Natl Acad. Sci. USA, 98, 6571-6576.
43. Heinrich, B., Zhang, Z., Raitskin, O., Hiller, M., Benderska, N., Hartmann, A.M., Bracco, L., Elliott, D., Ben-Ari, S., Soreq, H. et al. (2009) Heterogeneous nuclear ribonucleoprotein G regulates splice site selection by binding to CC(A/C)-rich regions in pre-mRNA. J. Biol. Chem., 284, 14303-14315.
44. Reuter, J.S. and Mathews, D.H. (2010) RNAstructure: software for RNA secondary structure prediction and analysis. BMC Bioinformatics, 11, 129.
45. Hofacker, I.L. (2003) Vienna RNA secondary structure server. Nucleic Acids Res., 31, 3429-3431.
46. Turner, D.H. and Mathews, D.H. (2010) NNDB: the nearest neighbor parameter database for predicting stability of nucleic acid secondary structure. Nucleic Acids Res., 38, D280-D282.
47. Varani, L., Spillantini, M.G., Goedert,M. and Varani, G. (2000) Structural basis for recognition of the RNA major groove in the tau exon 10 splicing regulatory element by aminoglycoside antibiotics. Nucleic Acids Research, 28, 710-719.
48. Schirle, N.T., Goodman, R.A., Krishnamurthy,M. and Beal, P.A. (2010) Selective inhibition of ADAR2-catalyzed editing of the serotonin 2c receptor pre-mRNA by a helix-threading peptide. Org. Biomol. Chem., 8, 4898-4904.
49. Connolly, H.M., Crary, J.L., McGoon, M.D., Hensrud, D.D., Edwards, B.S., Edwards, W.D. and Schaff, H.V. (1997) Valvular heart disease associated with fenfluramine-phentermine. N. Engl. J. Med., 337, 581-588.
50. Bocobza, S., Adato, A., Mandel, T., Shapira, M., Nudler,E. and Aharoni, A. (2007) Riboswitch-dependent gene regulation and its evolution in the plant kingdom. Genes Dev., 21, 2874-2879.