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Prepublished online as a Blood First Edition Paper on January 9, 2003; DOI 10.1182/blood-2002-06-1796. This Article Full Text (PDF) All Versions of this Article: 2002-06-1796v1 101/10/4164    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Parra, M. K Articles by Conboy, J. G Search for Related Content PubMed PubMed Citation Articles by Parra, M. K Articles by Conboy, J. G Social Bookmarking                   What's this? Submitted June 17, 2002 Accepted December 27, 2002 Alternative 5' exons and differential splicing regulate expression of protein 4.1R isoforms with distinct N-termini Marilyn K Parra, Sherry L Gee, Mark J Koury, Mohandas Narla, and John G Conboy* Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA New York Blood Center, New York, NY, USA Department of Medicine, Vanderbilt University, Veterans Affairs Medical Centers, Nashville, TN, USA * Corresponding author; email: JGConboy{at}lbl.gov. Among the alternative pre-mRNA splicing events that characterize protein 4.1R gene expression, one involving exon 2' plays a critical role in regulating translation initiation and N-terminal protein structure. Exon 2' encompasses translation initiation site AUG1 and is located between alternative splice acceptor sites at the 5' end of exon 2; its inclusion or exclusion from mature 4.1R mRNA regulates expression of longer or shorter isoforms of 4.1R protein, respectively. The current study reports unexpected complexity in the 5' region of the 4.1R gene that directly affects alternative splicing of exon 2'. Three mutually exclusive alternative 5' exons, designated 1A, 1B, and 1C, were identified far upstream of exon 2 in both mouse and human genomes; all three are associated with strong transcriptional promoters in the flanking genomic sequence. Importantly, exons 1A and 1B splice differentially with respect to exon 2', generating transcripts with different 5' ends and distinct N-terminal protein coding capacity. Exon 1A-type transcripts splice so as to exclude exon 2' and therefore utilize the downstream AUG2 for translation of 80kD 4.1R protein, whereas exon 1B transcripts include exon 2' and initiate at AUG1 to synthesize 135kD isoforms. RNA blot analyses revealed that 1A transcripts increase in abundance in late erythroblasts, consistent with the previously demonstrated upregulation of 80kD 4.1R during terminal erythroid differentiation. Together these results suggest that synthesis of structurally distinct 4.1R protein isoforms in various cell types is regulated by a novel mechanism requiring coordination between upstream transcription initiation events and downstream alternative splicing events. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S.-C. Huang, A. Cho, S. Norton, E. S. Liu, J. Park, A. Zhou, I. D. Munagala, A. C. Ou, G. Yang, A. Wickrema, et al. Coupled transcription-splicing regulation of mutually exclusive splicing events at the 5' exons of protein 4.1R gene Blood, November 5, 2009; 114(19): 4233 - 4242. [Abstract] [Full Text] [PDF] L. A. Steiner, Y. Maksimova, V. Schulz, C. Wong, D. Raha, M. C. Mahajan, S. M. Weissman, and P. G. Gallagher Chromatin Architecture and Transcription Factor Binding Regulate Expression of Erythrocyte Membrane Protein Genes Mol. Cell. Biol., October 15, 2009; 29(20): 5399 - 5412. 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