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--AU-- Baklouti, F.; Huang, S. C.; Tang, T. K.; Delaunay, J.; Marchesi, V. T.; Benz, E. J.
--TI-- Asynchronous Regulation OF Splicing Events Within Protein 4.1 Pre-mrna During Erythroid Differentiation
--ST-- Blood
--YP-- 1996
--VL-- 87
--NB-- 9
--PS-- 3934
--PE-- 3941
--KW-- Membrane skeletal protein-4.1; Insertion deletion mutations; Actin binding domain; Molecular analysis; Hereditary elliptocytosis; Expression; Spectrin; Cells; Rna; Isoforms
--RT-- Journal Article
--TW-- Article
--QT-- Clinical medicine.
--IS-- 0006-4971
--AB-- Protein 4.1 is an 80-kD structural component of the red blood cell (RBC) cytoskeleton. It is critical for the formation of the spectrin/actin/protein 4.1 junctional complex, the integrity of which is important for the horizontal strength and elasticity of RBCs. We and others have previously shown that multiple protein 4.1 mRNA isoforms are generated from a single genomic locus by several alternative mRNA splicing events, leading to the insertion or skipping of discrete internal sequence motifs. The physiologic significance of these splicing events has been established for only two of these motifs: (1) an upstream 17-nucleotide sequence located at the 5' end of exon 2 that contains an in-frame ATG initiation codon, the inclusion of which by use of an alternative splice acceptor site in exon 2 allows the production of a 135-kD high-molecular-weight isoform present in nonerythroid cells; (2) exon 16, which encodes a 21-amino acid (21aa) segment located in the 10-kD ''spectrin/actin binding domain'' (SAB), the presence of which is required for junctional complex stability in RBCs. Previous studies by our group and others suggested that, among blood cells, this exon was retained only in mature mRNA in the erythroid lineage. Exon 16 is one of a series of three closely linked alternatively spliced exons, generating eight possible mRNA products with unique configurations of the SAB. In this communication, we report studies of the expression of both the translation initiation region and the SAB region during induced erythroid maturation in mouse erythroleukemia (MEL) cells. We have found that only two of eight possible combinatorial patterns of exon splicing at the SAB region are encountered: the isoform lacking all three exons, present in predifferentiated cells, and the isoform containing only exon 16, which increases in amount during erythroid differentiation. The proteinisoform containing the 21aa segment encoded by exon 16 efficiently and exclusively incorporates into the membrane, whereas the isoform lacking this 21aa segment remains in the cytoplasm, as well as the membrane.
--AD-- Reprint available from: Baklouti F INST PASTEUR LYON CNRS URA 1171 AVE TONY GARNIER F-69365 LYON 07 FRANCE YALE UNIV DEPT INTERNAL MED NEW HAVEN,CT USA YALE UNIV DEPT PATHOL NEW HAVEN, CT USA YALE
--LG-- English
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