Alternate processing of Flt1 transcripts is directed by conserved cis-elements within an intronic region of FLT1 that reciprocally regulates splicing and polyadenylation

Nucleic Acids Research

Volumn 38, Issue 15, 2010, Pages 5130-5140

  Thomas, Christie P ^a,b   Raikwar, Nandita S ^a   Kelley, Elizabeth A ^a   Liu, Kang Z ^a  

^a UNIVERSITY OF IOWA   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA; POLYADENYLIC ACID; VASCULOTROPIN RECEPTOR 1; REGULATORY RNA SEQUENCE;

ALTERNATIVE RNA SPLICING; ARTICLE; CELL STRAIN COS7; CONTROLLED STUDY; CYTOTROPHOBLAST; ENDOTHELIUM CELL; EXON; GENE DELETION; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; INTRON; MUTATIONAL ANALYSIS; POLYADENYLATION; PRIORITY JOURNAL; RNA PROCESSING; ANIMAL; CELL CULTURE; CHLOROCEBUS AETHIOPS; COS 1 CELL LINE; CYTOLOGY; GENETICS; METABOLISM; NUCLEOTIDE SEQUENCE; REGULATORY RNA SEQUENCE; TROPHOBLAST; VASCULAR ENDOTHELIUM;

ALTERNATIVE SPLICING; ANIMALS; BASE SEQUENCE; CELLS, CULTURED; CERCOPITHECUS AETHIOPS; CONSERVED SEQUENCE; COS CELLS; ENDOTHELIUM, VASCULAR; HUMANS; INTRONS; POLYADENYLATION; REGULATORY SEQUENCES, RIBONUCLEIC ACID; TROPHOBLASTS; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1;

EID: 77956096765     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkq198     Document Type: Article

References (24)

1. Cross, M.J., Dixelius, J., Matsumoto, T. and Claesson-Welsh, L. (2003) VEGF-receptor signal transduction. Trends Biochem. Sci., 28, 488-494.
2. Tammela, T., Enholm, B., Alitalo, K. and Paavonen, K. (2005) The biology of vascular endothelial growth factors. Cardiovasc. Res., 65, 550-563.
3. Roskoski, R. Jr (2008) VEGF receptor protein-tyrosine kinases: structure and regulation. Biochem. Biophys. Res. Commun., 375, 287-291.
4. Ambati, B.K., Nozaki, M., Singh, N., Takeda, A., Jani, P.D., Suthar, T., Albuquerque, R.J.C., Richter, E., Sakurai, E., Newcomb, M.T. et al. (2006) Corneal avascularity is due to soluble VEGF receptor-1. Nature, 443, 993.
5. Chappell, J.C., Taylor, S.M., Ferrara, N. and Bautch, V.L. (2009) Local guidance of emerging vessel sprouts requires soluble Flt-1. Dev. Cell, 17, 377-386.
6. Maynard, S.E., Min, J.Y., Merchan, J., Lim, K.H., Li, J., Mondal, S., Libermann, T.A., Morgan, J.P., Sellke, F.W., Stillman, I.E. et al. (2003) Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J. Clin. Invest., 111, 649-658.
7. Sugimoto, H., Hamano, Y., Charytan, D., Cosgrove, D., Kieran, M., Sudhakar, A. and Kalluri, R. (2003) Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria. J. Biol. Chem., 278, 12605-12608.
8. Suzuki, H., Ohkuchi, A., Matsubara, S., Takei, Y., Murakami, M., Shibuya, M., Suzuki, M. and Sato, Y. (2009) Effect of recombinant placental growth factor 2 on hypertension induced by full-length mouse soluble fms-like tyrosine kinase 1 adenoviral vector in pregnant mice. Hypertension, 54, 1129-1135.
9. Kendall, R.L. and Thomas, K.A. (1993) Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc. Natl Acad. Sci. USA, 90, 10705-10709.
10. Kondo, K., Hiratsuka, S., Subbalakshmi, E., Matsushime, H. and Shibuya, M. (1998) Genomic organization of the flt-1 gene encoding for vascular endothelial growth factor (VEGF) receptor-1 suggests an intimate evolutionary relationship between the 7-Ig and the 5-Ig tyrosine kinase receptors. Gene, 208, 297-305.
11. Thomas, C.P., Andrews, J.I. and Liu, K.Z. (2007) Intronic polyadenylation signal sequences and alternate splicing generate human soluble Flt1 variants and regulate the abundance of soluble Flt1 in the placenta. FASEB J., 21, 3885-3895.
12. Sela, S., Itin, A., Natanson-Yaron, S., Greenfield, C., Goldman-Wohl, D., Yagel, S. and Keshet, E. (2008) A novel human-specific soluble vascular endothelial growth factor receptor 1. Cell type-specific splicing and implications to vascular endothelial growth factor homeostasis and preeclampsia. Circ. Res., CIRCRESAHA. 108.171504.
13. Heydarian, M., McCaffrey, T., Florea, L., Yang, Z., Ross, M.M., Zhou, W. and Maynard, S.E. (2009) Novel splice variants of sFlt1 are upregulated in preeclampsia. Placenta, 30, 250-255.
14. Thomas, C.P., Andrews, J.I., Raikwar, N.S., Kelley, E.A., Herse, F., Dechend, R., Golos, T.G. and Liu, K.Z. (2009) A recently evolved novel trophoblast-enriched sFlt1 variant is upregulated in hypoxia and in preeclampsia. J. Clin. Endocrinol. Metab., 94, 2524-2530.
15. Zhou, Y., McMaster, M., Woo, K., Janatpour, M., Perry, J., Karpanen, T., Alitalo, K., Damsky, C. and Fisher, S.J. (2002) Vascular endothelial growth factor ligands and receptors that regulate human cytotrophoblast survival are dysregulated in severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. Am. J. Pathol., 160, 1405-1423.
16. Tsatsaris, V., Goffin, F., Munaut, C., Brichant, J.-F., Pignon, M.-R., Noel, A., Schaaps, J.-P., Cabrol, D., Frankenne, F. and Foidart, J.-M. (2003) Overexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences. J. Clin. Endocrinol. Metab., 88, 5555-5563.
17. Ahmad, S. and Ahmed, A. (2004) Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits angiogenesis in preeclampsia. Circ. Res., 95, 884-891.
18. Edwalds-Gilbert, G., Veraldi, K. and Milcarek, C. (1997) Alternative poly(A) site selection in complex transcription units: means to an end? Nucleic Acids Res., 25, 2547-2561.
19. Nelson, D.M., Johnson, R.D., Smith, S.D., Anteby, E.Y. and Sadovsky, Y. (1999) Hypoxia limits differentiation and up-regulates expression and activity of prostaglandin H synthase 2 in cultured trophoblast from term human placenta. Am. J. Obstet. Gynecol., 180, 896.
20. Sayegh, R., Auerbach, S.D., Li, X., Loftus, R., Husted, R., Stokes, J.B. and Thomas, C.P. (1999) Glucocorticoid induction of epithelial sodium channel expression in lung and renal epithelia occurs via trans-activation of a hormone response element in the 50 flanking region of the human epithelial sodium channel a subunit gene. J. Biol. Chem., 274, 12431-12437.
21. Tian, B., Hu, J., Zhang, H. and Lutz, C.S. (2005) A large-scale analysis of mRNA polyadenylation of human and mouse genes. Nucleic Acids Res., 33, 201-212.
22. Zhang, H., Lee, J. and Tian, B. (2005) Biased alternative polyadenylation in human tissues. Genome Biol., 6, R100.
23. Tian, B., Pan, Z. and Lee, J.Y. (2007) Widespread mRNA polyadenylation events in introns indicate dynamic interplay between polyadenylation and splicing. Genome Res., 17, 156-165.
24. 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.