|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 51, 50143-50154, December 20, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Renal-Electrolyte and Hypertension Division, Department of
Medicine, University of Pennsylvania School of Medicine,
Philadelphia, Pennsylvania 19104-6144
Alternative splicing of fibroblast growth factor
receptor 2 (FGFR2) mutually exclusive exons IIIb and IIIc represents a
tightly regulated and functionally relevant example of
post-transcriptional gene regulation. Rat prostate cancer DT3 and AT3
cell lines demonstrate exclusive selection of either exon IIIb or exon
IIIc, respectively, and have been used to characterize regulatory FGFR2
RNA cis-elements that are required for splicing regulation.
Two sequences termed ISE-2 and ISAR are located in the intron between
exons IIIb and IIIc and are required for cell-type specific exon IIIb.
Previous studies suggest that the function of these elements involves
formation of an RNA stem structure, even though they are separated by
more than 700 nucleotides. Using transfected minigenes, we performed a
systematic analysis of the sequence and structural components of ISE-2
and ISAR that are required for their ability to regulate FGFR2
splicing. We found that the primary sequence of these elements can be
replaced by completely unrelated sequences, provided that they are also
predicted to form an RNA stem structure. Thus, a nonsequence-specific
double stranded RNA stem constitutes a functional element
required for FGFR2 splicing; suggesting that a double-stranded RNA
binding protein is a component of the splicing regulatory machinery.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AYI61008 and AYI61009.
A Non-sequence-specific Double-stranded RNA Structural Element
Regulates Splicing of Two Mutually Exclusive Exons of Fibroblast Growth
Factor Receptor 2 (FGFR2)*
*
This work was supported by start-up funds from the
University of Pennsylvania School of Medicine, Department of Defense
Grant PC991539, and United States Public Health Services Grant K08
CA72560 from the NCI, National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: University of
Pennsylvania School of Medicine, 700 Clinical Research Bldg., 415 Curie
Blvd., Philadelphia, PA 19104-6144. Tel.: 215-573-1838; Fax:
215-898-0189; E-mail: russcars@mail.med.upenn.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Ohno, M. Hagiwara, and H. Kuroyanagi STAR family RNA-binding protein ASD-2 regulates developmental switching of mutually exclusive alternative splicing in vivo Genes & Dev., February 1, 2008; 22(3): 360 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Hovhannisyan and R. P. Carstens Heterogeneous Ribonucleoprotein M Is a Splicing Regulatory Protein That Can Enhance or Silence Splicing of Alternatively Spliced Exons J. Biol. Chem., December 14, 2007; 282(50): 36265 - 36274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. N. Singh, R. N. Singh, and E. J. Androphy Modulating role of RNA structure in alternative splicing of a critical exon in the spinal muscular atrophy genes Nucleic Acids Res., January 28, 2007; 35(2): 371 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kraunus, D. Zychlinski, T. Heise, M. Galla, J. Bohne, and C. Baum Murine Leukemia Virus Regulates Alternative Splicing through Sequences Upstream of the 5{middle dot} Splice Site J. Biol. Chem., December 8, 2006; 281(49): 37381 - 37390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. I. Bonano, S. Oltean, R. M. Brazas, and M. A. Garcia-Blanco Imaging the alternative silencing of FGFR2 exon IIIb in vivo RNA, December 1, 2006; 12(12): 2073 - 2079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Newman, S. J. Muh, R. H. Hovhannisyan, C. C. Warzecha, R. B. Jones, W. L. McKeehan, and R. P. Carstens Identification of RNA-binding proteins that regulate FGFR2 splicing through the use of sensitive and specific dual color fluorescence minigene assays RNA, June 1, 2006; 12(6): 1129 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Baraniak, J. R. Chen, and M. A. Garcia-Blanco Fox-2 Mediates Epithelial Cell-Specific Fibroblast Growth Factor Receptor 2 Exon Choice Mol. Cell. Biol., February 15, 2006; 26(4): 1209 - 1222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Hovhannisyan, C. C. Warzecha, and R. P. Carstens Characterization of sequences and mechanisms through which ISE/ISS-3 regulates FGFR2 splicing Nucleic Acids Res., January 12, 2006; 34(1): 373 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Glazov, M. Pheasant, E. A. McGraw, G. Bejerano, and J. S. Mattick Ultraconserved elements in insect genomes: A highly conserved intronic sequence implicated in the control of homothorax mRNA splicing Genome Res., June 1, 2005; 15(6): 800 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Canete-Soler, K. S. Reddy, D. R. Tolan, and J. Zhai Aldolases A and C Are Ribonucleolytic Components of a Neuronal Complex That Regulates the Stability of the Light-Neurofilament mRNA J. Neurosci., April 27, 2005; 25(17): 4353 - 4364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Wagner, A. P. Baraniak, O. M. Sessions, D. Mauger, E. Moskowitz, and M. A. Garcia-Blanco Characterization of the Intronic Splicing Silencers Flanking FGFR2 Exon IIIb J. Biol. Chem., April 8, 2005; 280(14): 14017 - 14027. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Hovhannisyan and R. P. Carstens A Novel Intronic cis Element, ISE/ISS-3, Regulates Rat Fibroblast Growth Factor Receptor 2 Splicing through Activation of an Upstream Exon and Repression of a Downstream Exon Containing a Noncanonical Branch Point Sequence Mol. Cell. Biol., January 1, 2005; 25(1): 250 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Buratti and F. E. Baralle Influence of RNA Secondary Structure on the Pre-mRNA Splicing Process Mol. Cell. Biol., December 15, 2004; 24(24): 10505 - 10514. [Full Text] [PDF]
|
|
|
|
|
|
E. Buratti, A. F. Muro, M. Giombi, D. Gherbassi, A. Iaconcig, and F. E. Baralle RNA Folding Affects the Recruitment of SR Proteins by Mouse and Human Polypurinic Enhancer Elements in the Fibronectin EDA Exon Mol. Cell. Biol., February 1, 2004; 24(3): 1387 - 1400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Baraniak, E. L. Lasda, E. J. Wagner, and M. A. Garcia-Blanco A Stem Structure in Fibroblast Growth Factor Receptor 2 Transcripts Mediates Cell-Type-Specific Splicing by Approximating Intronic Control Elements Mol. Cell. Biol., December 15, 2003; 23(24): 9327 - 9337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Gualandi, C Trabanelli, P Rimessi, E Calzolari, L Toffolatti, T Patarnello, G Kunz, F Muntoni, and A Ferlini Multiple exon skipping and RNA circularisation contribute to the severe phenotypic expression of exon 5 dystrophin deletion J. Med. Genet., August 1, 2003; 40(8): e100 - 100. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |