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hnRNP H and hnRNP F complex with Fox2 to silence fibroblast growth factor receptor 2 exon IIIc.
Mol Cell Biol. 2008 Sep; 28(17):5403-19.MC

Abstract

The heterogeneous nuclear ribonucleoprotein H (hnRNP) family of proteins has been shown to activate exon inclusion by binding intronic G triplets. Much less is known, however, about how hnRNP H and hnRNP F silence exons. In this study, we identify hnRNP H and hnRNP F proteins as being novel silencers of fibroblast growth factor receptor 2 exon IIIc. In cells that normally include this exon, we show that the overexpression of either hnRNP H1 or hnRNP F resulted in the dramatic silencing of exon IIIc. In cells that normally skip exon IIIc, skipping was disrupted when RNA interference was used to knock down both hnRNP H and hnRNP F. We show that an exonic GGG motif overlapped a critical exonic splicing enhancer, which was predicted to bind the SR protein ASF/SF2. Furthermore, the expression of ASF/SF2 reversed the silencing of exon IIIc caused by the expression of hnRNP H1. We show that hnRNP H and hnRNP F proteins are present in a complex with Fox2 and that the presence of Fox allows hnRNP H1 to better compete with ASF/SF2 for binding to exon IIIc. These results establish hnRNP H and hnRNP F as being repressors of exon inclusion and suggest that Fox proteins enhance their ability to antagonize ASF/SF2.

Authors+Show Affiliations

Box 3053 (424 CARL), Duke University Medical Center, Research Drive, Durham, NC 27710, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18573884

Citation

Mauger, David M., et al. "HnRNP H and hnRNP F Complex With Fox2 to Silence Fibroblast Growth Factor Receptor 2 Exon IIIc." Molecular and Cellular Biology, vol. 28, no. 17, 2008, pp. 5403-19.
Mauger DM, Lin C, Garcia-Blanco MA. HnRNP H and hnRNP F complex with Fox2 to silence fibroblast growth factor receptor 2 exon IIIc. Mol Cell Biol. 2008;28(17):5403-19.
Mauger, D. M., Lin, C., & Garcia-Blanco, M. A. (2008). HnRNP H and hnRNP F complex with Fox2 to silence fibroblast growth factor receptor 2 exon IIIc. Molecular and Cellular Biology, 28(17), 5403-19. https://doi.org/10.1128/MCB.00739-08
Mauger DM, Lin C, Garcia-Blanco MA. HnRNP H and hnRNP F Complex With Fox2 to Silence Fibroblast Growth Factor Receptor 2 Exon IIIc. Mol Cell Biol. 2008;28(17):5403-19. PubMed PMID: 18573884.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - hnRNP H and hnRNP F complex with Fox2 to silence fibroblast growth factor receptor 2 exon IIIc. AU - Mauger,David M, AU - Lin,Carolina, AU - Garcia-Blanco,Mariano A, Y1 - 2008/06/23/ PY - 2008/6/25/pubmed PY - 2008/9/10/medline PY - 2008/6/25/entrez SP - 5403 EP - 19 JF - Molecular and cellular biology JO - Mol Cell Biol VL - 28 IS - 17 N2 - The heterogeneous nuclear ribonucleoprotein H (hnRNP) family of proteins has been shown to activate exon inclusion by binding intronic G triplets. Much less is known, however, about how hnRNP H and hnRNP F silence exons. In this study, we identify hnRNP H and hnRNP F proteins as being novel silencers of fibroblast growth factor receptor 2 exon IIIc. In cells that normally include this exon, we show that the overexpression of either hnRNP H1 or hnRNP F resulted in the dramatic silencing of exon IIIc. In cells that normally skip exon IIIc, skipping was disrupted when RNA interference was used to knock down both hnRNP H and hnRNP F. We show that an exonic GGG motif overlapped a critical exonic splicing enhancer, which was predicted to bind the SR protein ASF/SF2. Furthermore, the expression of ASF/SF2 reversed the silencing of exon IIIc caused by the expression of hnRNP H1. We show that hnRNP H and hnRNP F proteins are present in a complex with Fox2 and that the presence of Fox allows hnRNP H1 to better compete with ASF/SF2 for binding to exon IIIc. These results establish hnRNP H and hnRNP F as being repressors of exon inclusion and suggest that Fox proteins enhance their ability to antagonize ASF/SF2. SN - 1098-5549 UR - https://www.unboundmedicine.com/medline/citation/18573884/hnRNP_H_and_hnRNP_F_complex_with_Fox2_to_silence_fibroblast_growth_factor_receptor_2_exon_IIIc_ L2 - https://journals.asm.org/doi/10.1128/MCB.00739-08?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -