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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. 2005 Jan; 25(1):250-63.MC

Abstract

Mutually exclusive splicing of fibroblast growth factor receptor 2 (FGFR2) exons IIIb and IIIc yields two receptor isoforms, FGFR2-IIIb and -IIIc, with distinctly different ligand binding properties. Several RNA cis elements in the intron (intron 8) separating these exons have been described that are required for splicing regulation. Using a heterologous splicing reporter, we have identified a new regulatory element in this intron that confers cell-type-specific inclusion of an unrelated exon that mirrors its ability to promote cell-type-specific inclusion of exon IIIb. This element promoted inclusion of exon IIIb while at the same time silencing exon IIIc inclusion in cells expressing FGFR2-IIIb; hence, we have termed this element ISE/ISS-3 (for "intronic splicing enhancer-intronic splicing silencer 3"). Silencing of exon IIIc splicing by ISE/ISS-3 was shown to require a branch point sequence (BPS) using G as the primary branch nucleotide. Replacing a consensus BPS with A as the primary branch nucleotide resulted in constitutive splicing of exon IIIc. Our results suggest that the branch point sequence constitutes an important component that can contribute to the efficiency of exon definition of alternatively spliced cassette exons. Noncanonical branch points may thus facilitate cell-type-specific silencing of regulated exons by flanking cis elements.

Authors+Show Affiliations

University of Pennsylvania School of Medicine, 700 Clinical Research Building, 415 Curie Blvd., Philadelphia, PA 19104-6144, USA.No 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

15601847

Citation

Hovhannisyan, Ruben H., and Russ 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." Molecular and Cellular Biology, vol. 25, no. 1, 2005, pp. 250-63.
Hovhannisyan RH, Carstens RP. 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. 2005;25(1):250-63.
Hovhannisyan, R. H., & Carstens, R. P. (2005). 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. Molecular and Cellular Biology, 25(1), 250-63.
Hovhannisyan RH, Carstens RP. 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. 2005;25(1):250-63. PubMed PMID: 15601847.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Hovhannisyan,Ruben H, AU - Carstens,Russ P, PY - 2004/12/17/pubmed PY - 2005/1/19/medline PY - 2004/12/17/entrez SP - 250 EP - 63 JF - Molecular and cellular biology JO - Mol Cell Biol VL - 25 IS - 1 N2 - Mutually exclusive splicing of fibroblast growth factor receptor 2 (FGFR2) exons IIIb and IIIc yields two receptor isoforms, FGFR2-IIIb and -IIIc, with distinctly different ligand binding properties. Several RNA cis elements in the intron (intron 8) separating these exons have been described that are required for splicing regulation. Using a heterologous splicing reporter, we have identified a new regulatory element in this intron that confers cell-type-specific inclusion of an unrelated exon that mirrors its ability to promote cell-type-specific inclusion of exon IIIb. This element promoted inclusion of exon IIIb while at the same time silencing exon IIIc inclusion in cells expressing FGFR2-IIIb; hence, we have termed this element ISE/ISS-3 (for "intronic splicing enhancer-intronic splicing silencer 3"). Silencing of exon IIIc splicing by ISE/ISS-3 was shown to require a branch point sequence (BPS) using G as the primary branch nucleotide. Replacing a consensus BPS with A as the primary branch nucleotide resulted in constitutive splicing of exon IIIc. Our results suggest that the branch point sequence constitutes an important component that can contribute to the efficiency of exon definition of alternatively spliced cassette exons. Noncanonical branch points may thus facilitate cell-type-specific silencing of regulated exons by flanking cis elements. SN - 0270-7306 UR - https://www.unboundmedicine.com/medline/citation/15601847/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_ L2 - http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=15601847 DB - PRIME DP - Unbound Medicine ER -