Evolutionarily conserved coupling of transcription and alternative splicing in the EPB41 (protein 4.1R) and EPB41L3 (protein 4.1B) genes.
Recent studies have shown that transcription and alternative splicing can be mechanistically coupled. In the EPB41 (protein 4.1R) and EPB41L3 (protein 4.1B) genes, we showed previously that promoter/alternative first exon choice is coupled to downstream splicing events in exon 2. Here we demonstrate that this coupling is conserved among several vertebrate classes from fish to mammals. The EPB41 and EPB41L3 genes from fish, bird, amphibian, and mammal genomes exhibit shared features including alternative first exons and differential splice acceptors in exon 2. In all cases, the 5'-most exon (exon 1A) splices exclusively to a weaker internal acceptor site in exon 2, skipping a fragment designated as exon 2'. Conversely, alternative first exons 1B and 1C always splice to the stronger first acceptor site, retaining exon 2'. These correlations are independent of cell type or species of origin. Since exon 2' contains a translation initiation site, splice variants generate protein isoforms with distinct N-termini. We propose that these genes represent a physiologically relevant model system for mechanistic analysis of transcription-coupled alternative splicing.
Tan
Jeff S
JS
Life Sciences Division and Genomics Department, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Mohandas
Narla
N
Conboy
John G
JG
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D003598:Cytoskeletal Proteins; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D013045:Species Specificity; D014158:Transcription, Genetic / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014714:Vertebrates / Q000235:genetics*
D001798:Blood Proteins; D003598:Cytoskeletal Proteins; C116887:EPB41L3 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; C028841:erythrocyte membrane band 4.1 protein