title: Alternative splicing generates variants in important functional domains of human slow skeletal troponin T.
abstract: We provide the first nucleotide sequence information for the slow isoform of troponin T (TnT). Sequence and hybridization analyses revealed that a single slow TnT gene present in the human genome gives rise to at least two different slow TnT variants by alternative splicing. The observed variations in slow TnT splicing generated major structural differences between the two corresponding slow TnT proteins in a domain that is likely to be involved in critical interactions with troponin C, troponin I, and tropomyosin in the thin filament. Corresponding variations have not been found for fast or for cardiac TnT. The comparison of splicing patterns for fast, cardiac, and slow TnT reveals that the splicing pattern for each isoform is unique. These features raise important questions of why and how all the individual members of the closely related TnT gene family developed such complex but different schemes of alternative splicing to create sets of variant proteins. This unusual familial trait is not known in any other muscle or nonmuscle multigene family.
authors.affiliation: Department of Medicine, Stanford Medical School, California.
authors.forename: R
authors.initials: R
authors.lastname: Gahlmann
authors.forename: A B
authors.initials: AB
authors.lastname: Troutt
authors.forename: R P
authors.initials: RP
authors.lastname: Wade
authors.forename: P
authors.initials: P
authors.lastname: Gunning
authors.forename: L
authors.initials: L
authors.lastname: Kedes
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004262:DNA Restriction Enzymes; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D012326:RNA Splicing; D014336:Troponin / Q000235:genetics*; D020107:Troponin T
chemical_list: D014336:Troponin; D020107:Troponin T; D004247:DNA; D004262:DNA Restriction Enzymes