The Splicing Regulatory Element, UGCAUG, is Phylogenetically and Spatially Conserved in Introns That Flank Tissue-specific Alternative Exons

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2005 Feb 5

PMID 15691898

Citations 65

Authors

Simon Minovitsky

Sherry L Gee

Shiruyeh Schokrpur

Inna Dubchak

John G Conboy

Affiliations

Soon will be listed here.

Abstract

Previous studies have identified UGCAUG as an intron splicing enhancer that is frequently located adjacent to tissue-specific alternative exons in the human genome. Here, we show that UGCAUG is phylogenetically and spatially conserved in introns that flank brain-enriched alternative exons from fish to man. Analysis of sequence from the mouse, rat, dog, chicken and pufferfish genomes revealed a strongly statistically significant association of UGCAUG with the proximal intron region downstream of brain-enriched alternative exons. The number, position and sequence context of intronic UGCAUG elements were highly conserved among mammals and in chicken, but more divergent in fish. Control datasets, including constitutive exons and non-tissue-specific alternative exons, exhibited a much lower incidence of closely linked UGCAUG elements. We propose that the high sequence specificity of the UGCAUG element, and its unique association with tissue-specific alternative exons, mark it as a critical component of splicing switch mechanism(s) designed to activate a limited repertoire of splicing events in cell type-specific patterns. We further speculate that highly conserved UGCAUG-binding protein(s) related to the recently described Fox-1 splicing factor play a critical role in mediating this specificity.

Citing Articles

Rbfox1 controls alternative splicing of focal adhesion genes in cardiac muscle cells.

Zorn P, Calvo Sanchez J, Alakhras T, Schreier B, Gekle M, Huttelmaier S J Mol Cell Biol. 2024; 16(1).

PMID: 38253401 PMC: 11216089. DOI: 10.1093/jmcb/mjae003.

Hypoplastic Left Heart Syndrome: Signaling & Molecular Perspectives, and the Road Ahead.

Datta S, Cao W, Skillman M, Wu M Int J Mol Sci. 2023; 24(20).

PMID: 37894928 PMC: 10607600. DOI: 10.3390/ijms242015249.

Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction.

Farshadyeganeh P, Nazim M, Zhang R, Ohkawara B, Nakajima K, Rahman M iScience. 2023; 26(10):107746.

PMID: 37744035 PMC: 10514471. DOI: 10.1016/j.isci.2023.107746.

RBFOX2-regulated TEAD1 alternative splicing plays a pivotal role in Hippo-YAP signaling.

Choi S, Lee H, Cho N, Kim I, Cheon S, Park C Nucleic Acids Res. 2022; 50(15):8658-8673.

PMID: 35699208 PMC: 9410899. DOI: 10.1093/nar/gkac509.

Systematic characterization of short intronic splicing-regulatory elements in SMN2 pre-mRNA.

Gao Y, Lin K, Jiang T, Yang Y, Rahman M, Gong S Nucleic Acids Res. 2022; 50(2):731-749.

PMID: 35018432 PMC: 8789036. DOI: 10.1093/nar/gkab1280.

References

Zhu J, Mayeda A, Krainer A . Exon identity established through differential antagonism between exonic splicing silencer-bound hnRNP A1 and enhancer-bound SR proteins. Mol Cell. 2002; 8(6):1351-61. DOI: 10.1016/s1097-2765(01)00409-9. View

Melot T, Dauphinot L, Sevenet N, Radvanyi F, Delattre O . Characterization of a new brain-specific isoform of the EWS oncoprotein. Eur J Biochem. 2001; 268(12):3483-9. DOI: 10.1046/j.1432-1327.2001.02251.x. View

Laura R, Ross S, Koeppen H, Lasky L . MAGI-1: a widely expressed, alternatively spliced tight junction protein. Exp Cell Res. 2002; 275(2):155-70. DOI: 10.1006/excr.2002.5475. View

Burgess H, Reiner O . Alternative splice variants of doublecortin-like kinase are differentially expressed and have different kinase activities. J Biol Chem. 2002; 277(20):17696-705. DOI: 10.1074/jbc.M111981200. View

Fairbrother W, Yeh R, Sharp P, Burge C . Predictive identification of exonic splicing enhancers in human genes. Science. 2002; 297(5583):1007-13. DOI: 10.1126/science.1073774. View

Rahman L, Bliskovski V, Reinhold W, Zajac-Kaye M . Alternative splicing of brain-specific PTB defines a tissue-specific isoform pattern that predicts distinct functional roles. Genomics. 2002; 80(3):245-9. DOI: 10.1006/geno.2002.6826. View

Forch P, Puig O, Martinez C, Seraphin B, Valcarcel J . The splicing regulator TIA-1 interacts with U1-C to promote U1 snRNP recruitment to 5' splice sites. EMBO J. 2002; 21(24):6882-92. PMC: 139089. DOI: 10.1093/emboj/cdf668. View

Jin Y, Suzuki H, Maegawa S, Endo H, Sugano S, Hashimoto K . A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUG. EMBO J. 2003; 22(4):905-12. PMC: 145449. DOI: 10.1093/emboj/cdg089. View

Rooke N, Markovtsov V, Cagavi E, Black D . Roles for SR proteins and hnRNP A1 in the regulation of c-src exon N1. Mol Cell Biol. 2003; 23(6):1874-84. PMC: 149473. DOI: 10.1128/MCB.23.6.1874-1884.2003. View

10.

Gromak N, Matlin A, Cooper T, Smith C . Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein. RNA. 2003; 9(4):443-56. PMC: 1370411. DOI: 10.1261/rna.2191903. View

11.

Kim S, Shi H, Lee D, Lis J . Specific SR protein-dependent splicing substrates identified through genomic SELEX. Nucleic Acids Res. 2003; 31(7):1955-61. PMC: 152802. DOI: 10.1093/nar/gkg286. View

12.

Nurtdinov R, Artamonova I, Mironov A, Gelfand M . Low conservation of alternative splicing patterns in the human and mouse genomes. Hum Mol Genet. 2003; 12(11):1313-20. DOI: 10.1093/hmg/ddg137. View

13.

Cartegni L, Wang J, Zhu Z, Zhang M, Krainer A . ESEfinder: A web resource to identify exonic splicing enhancers. Nucleic Acids Res. 2003; 31(13):3568-71. PMC: 169022. DOI: 10.1093/nar/gkg616. View

14.

Sorek R, Ast G . Intronic sequences flanking alternatively spliced exons are conserved between human and mouse. Genome Res. 2003; 13(7):1631-7. PMC: 403736. DOI: 10.1101/gr.1208803. View

15.

Ule J, Jensen K, Ruggiu M, Mele A, Ule A, Darnell R . CLIP identifies Nova-regulated RNA networks in the brain. Science. 2003; 302(5648):1212-5. DOI: 10.1126/science.1090095. View

16.

Zhang X, Heller K, Hefter I, Leslie C, Chasin L . Sequence information for the splicing of human pre-mRNA identified by support vector machine classification. Genome Res. 2003; 13(12):2637-50. PMC: 403805. DOI: 10.1101/gr.1679003. View

17.

Sorek R, Shamir R, Ast G . How prevalent is functional alternative splicing in the human genome?. Trends Genet. 2004; 20(2):68-71. DOI: 10.1016/j.tig.2003.12.004. View

18.

Sorek R, Lev-Maor G, Reznik M, Dagan T, Belinky F, Graur D . Minimal conditions for exonization of intronic sequences: 5' splice site formation in alu exons. Mol Cell. 2004; 14(2):221-31. DOI: 10.1016/s1097-2765(04)00181-9. View

19.

Zhang X, Chasin L . Computational definition of sequence motifs governing constitutive exon splicing. Genes Dev. 2004; 18(11):1241-50. PMC: 420350. DOI: 10.1101/gad.1195304. View

20.

Fairbrother W, Yeo G, Yeh R, Goldstein P, Mawson M, Sharp P . RESCUE-ESE identifies candidate exonic splicing enhancers in vertebrate exons. Nucleic Acids Res. 2004; 32(Web Server issue):W187-90. PMC: 441531. DOI: 10.1093/nar/gkh393. View