Alternative splicing as a therapeutic target for human diseases.
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.
Dery
Kenneth J
KJ
Division of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
Gusti
Veronica
V
Gaur
Shikha
S
Shively
John E
JE
Yen
Yun
Y
Gaur
Rajesh K
RK
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
D052157:Aptamers, Nucleotide; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; C065686:carcinoembryonic antigen binding protein, human; D013806:Theophylline