The ABCs of human alternative splicing: a review of ATP-binding cassette transporter splicing.
Human ATP-binding cassette (ABC) transporters are proteins that translocate solutes across cellular membranes. They are highly expressed in tissues that represent significant barriers of pharmacologic and toxicologic significance, such as the gastrointestinal tract, liver, kidney and brain, and therefore play a pivotal role in the absorption, distribution and excretion of xenobiotics and in host detoxification processes. This review explores the extent of alternative splicing of ABC transporters, based on studies of individual genes, genetic variation and sequence databases. Large-scale informatics studies have found multiple coding and non-coding splice isoforms for each transporter. While the importance of splicing in individual variation of drug response is not fully known, recent studies demonstrate that genetic mutations often induce alternative splicing of ABC transporters which may make certain individuals more susceptible to altered pharmacological and toxicological responses. Newer technologies such as exon/junction microarrays, multiplexed PCR assays and next generation sequencing may further clarify the relevance of ABC transporter splicing in drug development and disease management.
Srinivasan
Subha
S
Jivan Biologics Inc, Larkspur, CA 94939, USA. subha@jivanbio.com
Bingham
Jonathan L
JL
Johnson
Dale
D
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D017398:Alternative Splicing; D030541:Databases, Genetic; D064420:Drug-Related Side Effects and Adverse Reactions; D030342:Genetic Diseases, Inborn; D006801:Humans; D009154:Mutation; D004364:Pharmaceutical Preparations / Q000378:metabolism; D015262:Xenobiotics / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity
D018528:ATP-Binding Cassette Transporters; D004364:Pharmaceutical Preparations; D015262:Xenobiotics