Tags

Type your tag names separated by a space and hit enter

The nonsense-mediated decay pathway and mutually exclusive expression of alternatively spliced FGFR2IIIb and -IIIc mRNAs.
J Biol Chem. 2001 Feb 09; 276(6):4158-67.JB

Abstract

Exons IIIb and IIIc of the FGFR2 gene are alternatively spliced in a mutually exclusive manner in different cell types. A switch from expression of FGFR2IIIb to FGFR2IIIc accompanies the transition of nonmalignant rat prostate tumor epithelial cells (DTE) to cells comprising malignant AT3 tumors. Here we used transfection of minigenes with and without alterations in reading frame and with and without introns to examine how translation affects observed FGFR2 splice products. We observed that nonsense mutations in other than the last exon led to a dramatic reduction in mRNA that is abrogated by removal of downstream introns in both DTE and AT3 cells. The mRNA, devoid of both IIIb and IIIc exons (C1-C2), is a major splice product from minigenes lacking an intron downstream of the second common exon C2. From these observations, we suggest that repression of exon IIIc and activation of exon IIIb inclusion in DTE cells lead to the generation of both C1-IIIb-C2 and C1-C2 products. However, the C1-C2 product from the native gene is degraded due to a frameshift and a premature termination codon caused by splicing C1 and C2 together. Derepression of exon IIIc and repression of exon IIIb lead to the generation of both C1-IIIc-C2 and C1-C2 products in AT3 cells, but the C1-C2 product is degraded. The C1-IIIb-IIIc-C2 mRNA containing a premature termination codon in exon IIIc was present, but at apparently trace levels in both cell types. The nonsense-mediated mRNA decay pathway and cell type-dependent rates of inclusion of exons IIIb and IIIc result in the mutually exclusive expression of FGFR2IIIb and IIIc.

Authors+Show Affiliations

Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843-2128, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

11042206

Citation

Jones, R B., et al. "The Nonsense-mediated Decay Pathway and Mutually Exclusive Expression of Alternatively Spliced FGFR2IIIb and -IIIc MRNAs." The Journal of Biological Chemistry, vol. 276, no. 6, 2001, pp. 4158-67.
Jones RB, Wang F, Luo Y, et al. The nonsense-mediated decay pathway and mutually exclusive expression of alternatively spliced FGFR2IIIb and -IIIc mRNAs. J Biol Chem. 2001;276(6):4158-67.
Jones, R. B., Wang, F., Luo, Y., Yu, C., Jin, C., Suzuki, T., Kan, M., & McKeehan, W. L. (2001). The nonsense-mediated decay pathway and mutually exclusive expression of alternatively spliced FGFR2IIIb and -IIIc mRNAs. The Journal of Biological Chemistry, 276(6), 4158-67.
Jones RB, et al. The Nonsense-mediated Decay Pathway and Mutually Exclusive Expression of Alternatively Spliced FGFR2IIIb and -IIIc MRNAs. J Biol Chem. 2001 Feb 9;276(6):4158-67. PubMed PMID: 11042206.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The nonsense-mediated decay pathway and mutually exclusive expression of alternatively spliced FGFR2IIIb and -IIIc mRNAs. AU - Jones,R B, AU - Wang,F, AU - Luo,Y, AU - Yu,C, AU - Jin,C, AU - Suzuki,T, AU - Kan,M, AU - McKeehan,W L, Y1 - 2000/10/20/ PY - 2000/10/24/pubmed PY - 2001/6/22/medline PY - 2000/10/24/entrez SP - 4158 EP - 67 JF - The Journal of biological chemistry JO - J Biol Chem VL - 276 IS - 6 N2 - Exons IIIb and IIIc of the FGFR2 gene are alternatively spliced in a mutually exclusive manner in different cell types. A switch from expression of FGFR2IIIb to FGFR2IIIc accompanies the transition of nonmalignant rat prostate tumor epithelial cells (DTE) to cells comprising malignant AT3 tumors. Here we used transfection of minigenes with and without alterations in reading frame and with and without introns to examine how translation affects observed FGFR2 splice products. We observed that nonsense mutations in other than the last exon led to a dramatic reduction in mRNA that is abrogated by removal of downstream introns in both DTE and AT3 cells. The mRNA, devoid of both IIIb and IIIc exons (C1-C2), is a major splice product from minigenes lacking an intron downstream of the second common exon C2. From these observations, we suggest that repression of exon IIIc and activation of exon IIIb inclusion in DTE cells lead to the generation of both C1-IIIb-C2 and C1-C2 products. However, the C1-C2 product from the native gene is degraded due to a frameshift and a premature termination codon caused by splicing C1 and C2 together. Derepression of exon IIIc and repression of exon IIIb lead to the generation of both C1-IIIc-C2 and C1-C2 products in AT3 cells, but the C1-C2 product is degraded. The C1-IIIb-IIIc-C2 mRNA containing a premature termination codon in exon IIIc was present, but at apparently trace levels in both cell types. The nonsense-mediated mRNA decay pathway and cell type-dependent rates of inclusion of exons IIIb and IIIc result in the mutually exclusive expression of FGFR2IIIb and IIIc. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/11042206/The_nonsense_mediated_decay_pathway_and_mutually_exclusive_expression_of_alternatively_spliced_FGFR2IIIb_and__IIIc_mRNAs_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(18)46417-4 DB - PRIME DP - Unbound Medicine ER -