Coupled transcription-splicing regulation of mutually exclusive splicing events at the 5' exons of protein 4.1R gene
| Autor: | Shu-Ching Huang, Tang K. Tang, Eva S. Liu, Stephanie Norton, Aeri Cho, Jennie Park, Edward J. Benz, Anyu Zhou, Alexander C. Ou, Amittha Wickrema, Guang Yang, Indira D. Munagala |
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| Rok vydání: | 2009 |
| Předmět: |
Transcriptional Activation
Transcription Genetic Immunology Molecular Sequence Data Exonic splicing enhancer Biology Exon shuffling Biochemistry Cell Line Splicing factor Exon Mice Red Cells Iron and Erythropoiesis Tumor Cells Cultured Animals Humans Protein Isoforms Tissue Distribution Promoter Regions Genetic DNA Primers Genetics Splice site mutation Binding Sites Base Sequence Models Genetic Serine-Arginine Splicing Factors Alternative splicing Microfilament Proteins Membrane Proteins Nuclear Proteins RNA-Binding Proteins Cell Biology Hematology Blood Proteins DNA Polymerase II Exons Splicing Factor U2AF Alternative Splicing Cytoskeletal Proteins Ribonucleoproteins RNA splicing Leukemia Erythroblastic Acute 5' Untranslated Regions Minigene |
| Zdroj: | Blood. 114(19) |
| ISSN: | 1528-0020 |
| Popis: | The tightly regulated production of distinct erythrocyte protein 4.1R isoforms involves differential splicing of 3 mutually exclusive first exons (1A, 1B, 1C) to the alternative 3′ splice sites (ss) of exon 2′/2. Here, we demonstrate that exon 1 and 2′/2 splicing diversity is regulated by a transcription-coupled splicing mechanism. We also implicate distinctive regulatory elements that promote the splicing of exon 1A to the distal 3′ ss and exon 1B to the proximal 3′ ss in murine erythroleukemia cells. A hybrid minigene driven by cytomegalovirus promoter mimicked 1B-promoter–driven splicing patterns but differed from 1A-promoter–driven splicing patterns, suggesting that promoter identity affects exon 2′/2 splicing. Furthermore, splicing factor SF2/ASF ultraviolet (UV) cross-linked to the exon 2′/2 junction CAGAGAA, a sequence that overlaps the distal U2AF35-binding 3′ ss. Consequently, depletion of SF2/ASF allowed exon 1B to splice to the distal 3′ ss but had no effect on exon 1A splicing. These findings identify for the first time that an SF2/ASF binding site also can serve as a 3′ ss in a transcript-dependent manner. Taken together, our results suggest that 4.1R gene expression involves transcriptional regulation coupled with a complex splicing regulatory network. |
| Databáze: | OpenAIRE |
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