Restoration of the cystic fibrosis transmembrane conductance regulator function by splicing modulation.

ABSTRACT: A significant fraction of disease-causing mutations affects pre-mRNA splicing. These mutations can generate both aberrant and correct transcripts, the level of which varies among different patients. An inverse correlation was found between this level and disease severity, suggesting a role for splicing regulation as a genetic modifier. Overexpression of splicing factors increased the level of correctly spliced RNA, transcribed from minigenes carrying disease-causing splicing mutations. However, whether this increase could restore the protein function was unknown. Here, we demonstrate that overexpression of Htra2-beta1 and SC35 increases the level of normal cystic fibrosis transmembrane conductance regulator (CFTR) transcripts in cystic-fibrosis-derived epithelial cells carrying the 3849+10

SUBMITTER: Nissim-Rafinia M 

PROVIDER: S-EPMC1299168 | biostudies-literature | 2004 Nov

REPOSITORIES: biostudies-literature