Open AccessMolecular basis for modulation of biological function by alternate splicing of the Wilms' tumor suppressor protein
Author(s) -
John H. Laity,
H. Jane Dyson,
Peter E. Wright
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.97.22.11932
Subject(s) - zinc finger , rna splicing , linker , dna , suppressor , alternative splicing , biology , phd finger , microbiology and biotechnology , gene , chemistry , genetics , gene isoform , transcription factor , computer science , rna , operating system
Alternate splicing, leading to the insertion of the tripeptide KTS in the linker between the third and fourth C2 H2 zinc fingers, changes both the DNA-binding function and the subnuclear localization of the Wilms' tumor suppressor protein (WT1). We have used NMR relaxation experiments to determine the molecular basis for the differing DNA recognition properties of the WT1–KTS and WT1+KTS isoforms. Our results show that the KTS insertion increases the flexibility of the linker between fingers 3 and 4 and abrogates binding of the fourth zinc finger to its cognate site in the DNA major groove. This represents a mechanism whereby a single zinc-finger gene can be used, through alternate splicing, to fulfill different functions in the cell.