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5'- and 3'-terminal nucleotides in the FGFR2 ISAR splicing element core have overlapping roles in exon IIIb activation and exon IIIc repression.
Nucleic Acids Res. 2001 Sep 01; 29(17):3557-65.NA

Abstract

The cell type-specific, mutually-exclusive alternative splicing of the fibroblast growth factor receptor 2 (FGFR2) pre-mRNA is tightly regulated. A sequence termed ISAR (intronic splicing activator and repressor) has been implicated as an important cis regulatory element in both activation of exon IIIb and repression of exon IIIc splicing in epithelial cells. In order to better understand how this single sequence could have dual roles, we transfected minigenes containing a series of 2-bp mutations in the 18 3'-most nucleotides of ISAR that we refer to as the ISAR core. Transfection of cells with dual-exon (IIIb and IIIc) minigenes revealed that mutation of terminal sequences of the core led to decreased exon IIIb inclusion and increased exon IIIc inclusion. Transfection of cells with single-exon IIIb minigenes and single-exon IIIc minigenes revealed that mutation of terminal sequences of the ISAR core led to decreased exon IIIb inclusion and increased exon IIIc inclusion, respectively. Nucleotides of the ISAR core responsible for exon IIIb activation appear to overlap very closely with those required for exon IIIc repression. We describe a model in which ISAR and a 5' intronic sequence known as IAS2 form a stem structure required for simultaneous exon IIIb activation and exon IIIc repression.

Authors+Show Affiliations

Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11522825

Citation

Jones, R B., et al. "5'- and 3'-terminal Nucleotides in the FGFR2 ISAR Splicing Element Core Have Overlapping Roles in Exon IIIb Activation and Exon IIIc Repression." Nucleic Acids Research, vol. 29, no. 17, 2001, pp. 3557-65.
Jones RB, Carstens RP, Luo Y, et al. 5'- and 3'-terminal nucleotides in the FGFR2 ISAR splicing element core have overlapping roles in exon IIIb activation and exon IIIc repression. Nucleic Acids Res. 2001;29(17):3557-65.
Jones, R. B., Carstens, R. P., Luo, Y., & McKeehan, W. L. (2001). 5'- and 3'-terminal nucleotides in the FGFR2 ISAR splicing element core have overlapping roles in exon IIIb activation and exon IIIc repression. Nucleic Acids Research, 29(17), 3557-65.
Jones RB, et al. 5'- and 3'-terminal Nucleotides in the FGFR2 ISAR Splicing Element Core Have Overlapping Roles in Exon IIIb Activation and Exon IIIc Repression. Nucleic Acids Res. 2001 Sep 1;29(17):3557-65. PubMed PMID: 11522825.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5'- and 3'-terminal nucleotides in the FGFR2 ISAR splicing element core have overlapping roles in exon IIIb activation and exon IIIc repression. AU - Jones,R B, AU - Carstens,R P, AU - Luo,Y, AU - McKeehan,W L, PY - 2001/8/28/pubmed PY - 2001/9/21/medline PY - 2001/8/28/entrez SP - 3557 EP - 65 JF - Nucleic acids research JO - Nucleic Acids Res VL - 29 IS - 17 N2 - The cell type-specific, mutually-exclusive alternative splicing of the fibroblast growth factor receptor 2 (FGFR2) pre-mRNA is tightly regulated. A sequence termed ISAR (intronic splicing activator and repressor) has been implicated as an important cis regulatory element in both activation of exon IIIb and repression of exon IIIc splicing in epithelial cells. In order to better understand how this single sequence could have dual roles, we transfected minigenes containing a series of 2-bp mutations in the 18 3'-most nucleotides of ISAR that we refer to as the ISAR core. Transfection of cells with dual-exon (IIIb and IIIc) minigenes revealed that mutation of terminal sequences of the core led to decreased exon IIIb inclusion and increased exon IIIc inclusion. Transfection of cells with single-exon IIIb minigenes and single-exon IIIc minigenes revealed that mutation of terminal sequences of the ISAR core led to decreased exon IIIb inclusion and increased exon IIIc inclusion, respectively. Nucleotides of the ISAR core responsible for exon IIIb activation appear to overlap very closely with those required for exon IIIc repression. We describe a model in which ISAR and a 5' intronic sequence known as IAS2 form a stem structure required for simultaneous exon IIIb activation and exon IIIc repression. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/11522825/5'__and_3'_terminal_nucleotides_in_the_FGFR2_ISAR_splicing_element_core_have_overlapping_roles_in_exon_IIIb_activation_and_exon_IIIc_repression_ L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/29.17.3557 DB - PRIME DP - Unbound Medicine ER -