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A Non-sequence-specific double-stranded RNA structural element regulates splicing of two mutually exclusive exons of fibroblast growth factor receptor 2 (FGFR2).
J Biol Chem. 2002 Dec 20; 277(51):50143-54.JB

Abstract

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.

Authors+Show Affiliations

Renal-Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6144, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12393912

Citation

Muh, Stephanie J., et al. "A Non-sequence-specific Double-stranded RNA Structural Element Regulates Splicing of Two Mutually Exclusive Exons of Fibroblast Growth Factor Receptor 2 (FGFR2)." The Journal of Biological Chemistry, vol. 277, no. 51, 2002, pp. 50143-54.
Muh SJ, Hovhannisyan RH, Carstens RP. A Non-sequence-specific double-stranded RNA structural element regulates splicing of two mutually exclusive exons of fibroblast growth factor receptor 2 (FGFR2). J Biol Chem. 2002;277(51):50143-54.
Muh, S. J., Hovhannisyan, R. H., & Carstens, R. P. (2002). A Non-sequence-specific double-stranded RNA structural element regulates splicing of two mutually exclusive exons of fibroblast growth factor receptor 2 (FGFR2). The Journal of Biological Chemistry, 277(51), 50143-54.
Muh SJ, Hovhannisyan RH, Carstens RP. A Non-sequence-specific Double-stranded RNA Structural Element Regulates Splicing of Two Mutually Exclusive Exons of Fibroblast Growth Factor Receptor 2 (FGFR2). J Biol Chem. 2002 Dec 20;277(51):50143-54. PubMed PMID: 12393912.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Non-sequence-specific double-stranded RNA structural element regulates splicing of two mutually exclusive exons of fibroblast growth factor receptor 2 (FGFR2). AU - Muh,Stephanie J, AU - Hovhannisyan,Ruben H, AU - Carstens,Russ P, Y1 - 2002/10/21/ PY - 2002/10/24/pubmed PY - 2003/2/14/medline PY - 2002/10/24/entrez SP - 50143 EP - 54 JF - The Journal of biological chemistry JO - J Biol Chem VL - 277 IS - 51 N2 - 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/12393912/A_Non_sequence_specific_double_stranded_RNA_structural_element_regulates_splicing_of_two_mutually_exclusive_exons_of_fibroblast_growth_factor_receptor_2__FGFR2__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(19)33002-9 DB - PRIME DP - Unbound Medicine ER -