title: Alternative intronic promoters in development and disease.
abstract: Approximately 20,000 mammalian genes are estimated to encode between 250 thousand and 1 million different proteins. This enormous diversity of the mammalian proteome is caused by the ability of a single-gene locus to encode multiple protein isoforms. Protein isoforms encoded by one gene locus can be functionally distinct, and they can even have antagonistic functions. One of the mechanisms involved in creating this proteome complexity is alternative promoter usage. Alternative intronic promoters are located downstream from their canonical counterparts and drive the expression of alternative RNA isoforms that lack upstream exons. These upstream exons can encode some important functional domains, and proteins encoded by alternative mRNA isoforms can be thus functionally distinct from the full-length protein encoded by canonical mRNA isoforms. Since any misbalance of functionally distinct protein isoforms is likely to have detrimental consequences for the cell and the whole organism, their expression must be precisely regulated. Misregulation of alternative intronic promoters is frequently associated with various developmental defects and diseases including cancer, and it is becoming increasingly clear that this phenomenon deserves more attention.
authors.affiliation: Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Albertov 4, Praha 2, Czech Republic. tomas.vacik@lf1.cuni.cz.
authors.forename: Tomas
authors.identifier: http://orcid.org/0000-0003-0797-7757
authors.initials: T
authors.lastname: Vacik
authors.affiliation: Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Albertov 4, Praha 2, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Raska
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D005091:Exons / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger
keywords: Alternative promoters; Developmental defects; Gene expression; Human diseases; Protein isoforms; Transcriptional regulation