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Autoregulation of Fox protein expression to produce dominant negative splicing factors
Open accessAbstract
The Fox proteins are a family of regulators that control the alternative splicing of many exons in neurons, muscle, and other tissues. Each of the three mammalian paralogs, Fox-1 ( A2BP1 ), Fox-2 ( RBM9 ), and Fox-3 ( HRNBP3 ), produces proteins with a single RNA-binding domain (RRM) flanked by N- and C-terminal domains that are highly diversified through the use of alternative promoters and alternative splicing patterns. These genes also express protein isoforms lacking the second half of the RRM (FoxΔRRM), due to the skipping of a highly conserved 93-nt exon. Fox binding elements overlap the splice sites of these exons in Fox-1 and Fox-2, and the Fox proteins themselves inhibit exon inclusion. Unlike other cases of splicing autoregulation by RNA-binding proteins, skipping the RRM exon creates an in-frame deletion in the mRNA to produce a stable protein. These FoxΔRRM isoforms expressed from cDNA exhibit highly reduced binding to RNA in vivo. However, we show that they can act as repressors of Fox-dependent splicing, presumably by competing with full-length Fox isoforms for interaction with other splicing factors. Interestingly, the Drosophila Fox homolog contains a nearly identical exon in its RRM domain that also has flanking Fox-binding sites. Thus, rather than autoregulation of splicing controlling the abundance of the regulator, the Fox proteins use a highly conserved mechanism of splicing autoregulation to control production of a dominant negative isoform.
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“The mutually exclusive expression pattern of SLM1 and SLM2 is enforced by their cross-regulation via alternative splicing coupled with NMD, as seen with other paralogous pairs of RNA-binding proteins15,20,21,49,53,85,86.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [86]
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Cites
Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging
Mori, S., Crain, B. J., Chacko, V. P., & van Zijl, P. C. M. (1999) · Annals of Neurology · doi:10.1002/1531-8249(199902)45:2 · Cited by 3,513
Strong association of de novo copy number mutations with autism
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., et al. (2007) · Science · doi:10.1126/science.1138659 · Cited by 2,795
Lim, J., Hao, T., Shaw, C., Patel, A. J., Szabó, G., Rual, J.-F., Fisk, C. J., Li, N., Smolyar, A., Hill, D. E., et al. (2006) · Cell · doi:10.1016/j.cell.2006.03.032 · Cited by 789
Unproductive splicing of SR genes associated with highly conserved and ultraconserved DNA elements
Lareau, L. F., Inada, M., Green, R. E., Wengrod, J., & Brenner, S. E. (2007) · Nature · doi:10.1038/nature05676 · Cited by 685
Boutz, P. L., Stoilov, P., Li, Q., Lin, C.-H., Chawla, G., Ostrow, K., Shiue, L., Ares, M., & Black, D. L. (2007) · Genes & Development · doi:10.1101/gad.1558107 · Cited by 577
Self-citationYeo, G. W., Coufal, N. G., Liang, T. Y., Peng, G. E., Fu, X.-D., & Gage, F. H. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1545 · Cited by 572
Ni, J. Z., Grate, L. R., Donohue, J. P., Preston, C. G., Nobida, N., O’Brien, G. S., Shiue, L., Clark, T. A., Blume, J. E., & Ares, M. (2007) · Genes & Development · doi:10.1101/gad.1525507 · Cited by 551
Wollerton, M., Gooding, C., Wagner, E. J., García-Blanco, M. A., & Smith, C. W. J. (2004) · Molecular Cell · doi:10.1016/s1097-2765(03)00502-1 · Cited by 409
Kim, K. K., Adelstein, R. S., & Kawamoto, S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.052969 · Cited by 398
SC35 autoregulates its expression by promoting splicing events that destabilize its mRNAs
Sureau, A., Gattoni, R., Dooghe, Y., Ste'venin, J., & Soret, J. (2001) · EMBO Journal · doi:10.1093/emboj/20.7.1785 · Cited by 347
Spellman, R., Llorian, M., & Smith, C. W. J. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.06.016 · Cited by 313
Jin, Y., Suzuki, H., Maegawa, S., Endo, H., Sugano, S., Hashimoto, K., Yasuda, K., & Inoue, K. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg089 · Cited by 311
MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development
Boutz, P. L., Chawla, G., Stoilov, P., & Black, D. L. (2007) · Genes & Development · doi:10.1101/gad.1500707 · Cited by 304
Self-citationDefining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2
Zhang, C., Zhang, Z., Castle, J., Sun, S., Johnson, J., Krainer, A. R., & Zhang, M. Q. (2008) · Genes & Development · doi:10.1101/gad.1703108 · Cited by 300
Identification and analysis of alternative splicing events conserved in human and mouse
Yeo, G. W.-M., Nostrand, E. L. V., Holste, D., Poggio, T., & Burge, C. B. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409742102 · Cited by 299
Servadio, A., Koshy, B., Armstrong, D. L., Antalffy, B. A., Orr, H. T., & Zoghbi, H. Y. (1995) · Nature Genetics · doi:10.1038/ng0595-94 · Cited by 298
Multilevel Regulation of Gene Expression by MicroRNAs
Makeyev, E. V., & Maniatis, T. (2008) · Science · doi:10.1126/science.1152326 · Cited by 296
Intronic Sequences Flanking Alternatively Spliced Exons Are Conserved Between Human and MousePreprint
Sorek, R., & Ast, G. (2003) · Genome Research · doi:10.1101/gr.1208803 · Cited by 282
The splicing factor SRp20 modifies splicing of its own mRNA and ASF/SF2 antagonizes this regulation
Jumaa, H., & Nielsen, P. J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.16.5077 · Cited by 276
Homologues of the Caenorhabditis elegans Fox-1 Protein Are Neuronal Splicing Regulators in Mammals
Underwood, J. G., Boutz, P. L., Dougherty, J. D., Stoilov, P., & Black, D. L. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.22.10005-10016.2005 · Cited by 272
Self-citationMolecular basis of RNA recognition by the human alternative splicing factor Fox-1
Auweter, S. D., Fasan, R., Reymond, L., Underwood, J. G., Black, D. L., Pitsch, S., & Allain, F. H. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7600918 · Cited by 264
Self-citationA novel protein with RNA-binding motifs interacts with ataxin-2
Shibata, H. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.9.1303 · Cited by 221
Saltzman, A. L., Kim, Y. K., Pan, Q., Fagnani, M. M., Maquat, L. E., & Blencowe, B. J. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00361-08 · Cited by 204
Cytogenetic and molecular characterization of A2BP1/FOX1 as a candidate gene for autism
Martin, C. L., Duvall, J. A., Ilkin, Y., Simon, J. S., Arreaza, M. G., Wilkes, K., Alvarez‐Retuerto, A., Whichello, A., Powell, C. M., Rao, K., et al. (2007) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30530 · Cited by 198
Unusual Intron Conservation near Tissue-Regulated Exons Found by Splicing Microarrays
Sugnet, C. W., Srinivasan, K., Clark, T. A., O’Brien, G. S., Cline, M., Wang, H., Williams, A., Kulp, D., Blume, J. E., Haussler, D. H., et al. (2006) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0020004 · Cited by 197
Nakahata, S. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki338 · Cited by 182
Stoilov, P. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh051 · Cited by 180
Activation of c-src neuron-specific splicing by an unusual RNA element in vivo and in vitro
Black, D. L. (1992) · Cell · doi:10.1016/0092-8674(92)90291-j · Cited by 172
Self-citationMcKee, A. E., Minet, E., Stern, C., Riahi, S., Stiles, C. D., & Silver, P. A. (2005) · BMC Developmental Biology · doi:10.1186/1471-213x-5-14 · Cited by 166
Lee, J.-A., Tang, Z., & Black, D. L. (2009) · Genes & Development · doi:10.1101/gad.1837009 · Cited by 162
Self-citationRegulation of alternative pre-mRNA splicing by a novel repeated hexanucleotide element.Preprint
Huh, G. S., & Hynes, R. O. (1994) · Genes & Development · doi:10.1101/gad.8.13.1561 · Cited by 155
Tsai, C.-C., Kao, H.-Y., Mitzutani, A., Banayo, E., Rajan, H., McKeown, M., & Evans, R. (2004) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0400615101 · Cited by 147
Bhalla, K., Phillips, H. A., Crawford, J., McKenzie, O. L. D., Mulley, J. C., Eyre, H., Gardner, A. E., Kremmidiotis, G., & Callen, D. F. (2004) · Journal of Human Genetics · doi:10.1007/s10038-004-0145-4 · Cited by 146
Auto- and Cross-Regulation of the hnRNP L Proteins by Alternative Splicing
Rossbach, O., Hung, L.-H., Schreiner, S., Grishina, I., Heiner, M., Hui, J., & Bindereif, A. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01689-08 · Cited by 141
Modafferi, E. F., & Black, D. L. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.11.6537 · Cited by 132
Self-citationhnRNP H and hnRNP F Complex with Fox2 To Silence Fibroblast Growth Factor Receptor 2 Exon IIIc
Mauger, D., Lin, C., & García-Blanco, M. A. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00739-08 · Cited by 132
Nova autoregulation reveals dual functions in neuronal splicing
Dredge, B. K., Stefani, G., Engelhard, C. C., & Darnell, R. B. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600630 · Cited by 125
Ponthier, J. L., Schluepen, C., Chen, W., Lersch, R., Gee, S. L., Hou, V., Lo, A., Short, S. A., Chasis, J. A., Winkelmann, J. C., et al. (2006) · eScholarship (California Digital Library) · Cited by 119
Fox-2 Mediates Epithelial Cell-Specific Fibroblast Growth Factor Receptor 2 Exon Choice
Baraniak, A. P., Chen, J. R., & García-Blanco, M. A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.4.1209-1222.2006 · Cited by 118
X-chromosome-counting mechanisms that determine nematode sex
Nicoll, M., Akerib, C. C., & Meyer, B. J. (1997) · Nature · doi:10.1038/40669 · Cited by 108
Alternative Splicing of the Fibronectin EIIIB Exon Depends on Specific TGCATG Repeats
Lim, L. P., & Sharp, P. A. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.7.3900 · Cited by 107
Gatto–Konczak, F. D., Plet, A., Gesnel, M.-C., Fort, C., & Breathnach, R. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.9.5106 · Cited by 85
Developmental Control of CaV1.2 L-Type Calcium Channel Splicing by Fox Proteins
Tang, Z. Z., Zheng, S., Nikolic, J. M., & Black, D. L. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00608-09 · Cited by 84
Self-citationHodgkin, J., Zellan, J. D., & Albertson, D. G. (1994) · Development · doi:10.1242/dev.120.12.3681 · Cited by 77
Kawamoto, S. (1996) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)86956-9 · Cited by 74
Kubo, Y. (1991) · The Journal of Physiology · doi:10.1113/jphysiol.1991.sp018817 · Cited by 69
Deguillien, M., Huang, S., Morinière, M., Dreumont, N., Benz, E. J. J., & Baklouti, F. (2001) · Blood · doi:10.1182/blood.v98.13.3809 · Cited by 61
Identification and expression of a mouse ortholog of A2BP1
Kiehl, T., Shibata, H., Vo, T., Huynh, D., & Pulst, S. (2001) · Mammalian Genome · doi:10.1007/s00335-001-2056-4 · Cited by 55
Control of alternative pre-mRNA splicing by distributed pentameric repeats
Hedjran, F., Yeakley, J. M., Huh, G. S., Hynes, R. O., & Rosenfeld, M. G. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.23.12343 · Cited by 55
Negative feedback regulation among SR splicing factors encoded by Rbp1 and Rbp1‐like in Drosophila
Kumar, S., & Lopez, A. J. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600723 · Cited by 41
Regulated Fox-2 isoform expression mediates protein 4.1R splicing during erythroid differentiation
Yang, G., Huang, S.-C., Wu, J. Y., & Benz, E. J. J. (2007) · Blood · doi:10.1182/blood-2007-01-068940 · Cited by 39
Hase, M. E., Yalamanchili, P., & Visa, N. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604235200 · Cited by 28
Androgens Regulate the Mammalian Homologues of Invertebrate Sex Determination Genes tra-2 and fox-1
Lieberman, A. P., Friedlich, D. L., Harmison, G. G., Howell, B. W., Jordan, C. L., Breedlove, S. M., & Fischbeck, K. H. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.4617 · Cited by 28
Splicing-active nuclear extracts from rat brain
Grabowski, P. J. (2005) · Methods · doi:10.1016/j.ymeth.2005.07.014 · Cited by 16
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Lovci, M. T., Ghanem, D., Marr, H., Arnold, J., Gee, S., Parra, M., Liang, T. Y., Stark, T. J., Gehman, L. T., Hoon, S., et al. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2699 · Cited by 385
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“Its skipping as a result of autoregulation generates a dominantnegative form that lacks RNA binding capability (Baraniak et al., 2006; Damianov and Black, 2010).”
Metadata
- Authors
- Damianov, A., & Black, D. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2009-12-30
- Volume
- 16
- Issue
- 2
- Pages
- 405-416
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- PMC
- PMC2811669
- OpenAlex
- W2158982822
- Cited by
- 120
- References
- 54
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 7 · 2022: 9 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 15 · 2016: 10 · 2015: 5 · 2014: 8 · 2013: 13 · 2012: 10
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- RNA (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (RO1 GM49662)
- National Institute of General Medical Sciences (R01GM049662)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- alternative splicing, RRM domain, exon skipping, RNA-binding proteins, splicing repressor, alternative promoters, protein isoforms
- MeSH terms
- RNA Splicing Factors, Amino Acid Sequence, Animals, Base Sequence, Cell Line, Female, Homeostasis, Humans, Male, Molecular Sequence Data, Gene Expression, RNA-Binding Proteins, Sequence Homology, Amino Acid, Alternative Splicing, DNA Primers, Mice
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