title: Alternative splicing as a therapeutic target for human diseases.
abstract: The majority of eukaryotic genes undergo alternative splicing, an evolutionarily conserved phenomenon, to generate functionally diverse protein isoforms from a single transcript. The fact that defective pre-mRNA splicing can generate non-functional and often toxic proteins with catastrophic effects, accurate removal of introns and joining of exons is vital for cell homeostasis. Thus, molecular tools that could either silence a disease-causing gene or regulate its expression in trans will find many therapeutic applications. Here we present two RNA-based approaches, namely RNAi and theophylline-responsive riboswitch that can regulate gene expression by loss-of-function and modulation of splicing, respectively. These strategies are likely to continue to play an integral role in studying gene function and drug discovery.
authors.affiliation: Division of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Dery
authors.forename: Veronica
authors.initials: V
authors.lastname: Gusti
authors.forename: Shikha
authors.initials: S
authors.lastname: Gaur
authors.forename: John E
authors.initials: JE
authors.lastname: Shively
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Gaur
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects*; D052157:Aptamers, Nucleotide / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D013806:Theophylline / Q000378:metabolism / Q000494:pharmacology*; D014162:Transfection
chemical_list: D052157:Aptamers, Nucleotide; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; C065686:carcinoembryonic antigen binding protein, human; D013806:Theophylline